FR2853909A1 - Using polynucleotide probes based on the DPYSL3 gene (Dihydropyrimidinase-like 3), for diagnosis of psoriasis, or predisposition, and in screening for antipsoriatic agents - Google Patents

Abstract

Use of a polynucleotide probe (A) of 10-500 bp and at least 80% complementary with a target corresponding to all or part of the DPYSL3 (Dihydropyrimidinase-like 3) gene (NM 001387.1) (a) for characterizing a biological sample by measuring the level of DPYSL3 or (b) for identifying compounds (I) for treatment of psoriasis. Independent claims are also included for the following: (1) method for identifying (I); (2) research tool or diagnostic kit that comprises (A); (3) method for diagnosing psoriasis, or a predisposition to it, by measuring overexpression of DPYSL3, by contacting a test sample with (A). ACTIVITY : Antipsoriatic. No details of tests for antipsoriatic activity are given. MECHANISM OF ACTION : Hydrolase inhibitor; Dihydropyrimidinase-like 3 inhibitor; RNAi; RNA interference; Antisense oligonucleotide inhibitor.

Description

The subject of the present invention is the use of a probe relating to the

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  DPYSL3 for the characterization of a biological sample.

  The invention also relates to the use of this probe for the identification of a compound intended for the treatment of psoriasis, a method of identification as well as a new research tool.

  Psoriasis is a frequent dermatological pathology which affects 3 to 5% of the European population. Psoriasis is commonly associated with other pathologies, such as hypertension, arthritis, or AIDS (Farber EM, Nall L, In Roenigk HH, Maibach HI (Eds.): Psoriasis Third Edition, Revised and Expanded (1998), chapter 9: 107-157; Duvic M. et al., J Invest Dermatol (1990 Nov); 95 (5): 38S-40S).

  Based on the age of onset of symptoms and the association with certain genes of the major histocompatibility complex type I (MHC I), psoriasis has been classified into two subtypes called I and II ( Henseler T, Christophers E, In Roenigk HH, Maibach HI (Eds.): Psoriasis Third Edition, Revised and Expanded (1998), chapter 10: 159-166). Studies have also shown that 30 to 50% of patients with psoriasis have a family history in one of the 1st or 2nd degree parents. These observations have made it possible to suggest that psoriasis is a genetic disease with an autoimmune component (Bos, Br. J. Dermatol. (1988) 118: 141; Baadsgaard et al., J. Invest.

Dermatol. (1990) 95: 328).

  The main pathophysiological components of psoriasis include hyperproliferation associated with abnormal differentiation of keratinocytes of the epidermis, an inflammation characterized by an inflammatory infiltrate (mainly activated helper T lymphocytes) in the dermis and epidermis and by the release of proinflammatory cytokines, and finally an abnormal vascularization of the dermis (Krueger JG, J Am Acad Dermatol (2002) Jan; 46 (1): 1-23; quiz 23-6).

  The involvement of the inflammatory process in the pathophysiology of psoriasis is supported by the mechanism of action of certain agents having a therapeutic effect beneficial for the disease. For example, cyclosporine, used in the treatment of severe forms of psoriasis, exerts an inhibitory effect on the synthesis of interleukin-2, a cytokine promoting the proliferation of T lymphocytes and the secretion of inflammatory cytokines by these cells. Consequently, the modulators of inflammation make it possible to limit the inflammatory component characterizing in part psoriasis.

  Clinically, psoriasis is defined by hyperplasia of the epidermis, as well as by skin peeling, erythema and inflammation.

  Currently available methods of treatment include topical therapy, phototherapy, photo-chemotherapy and systemic therapy, reserved for the more severe forms of the disease. Nevertheless, these therapies only offer periods of remission to the patients, but the pathology generally resurfaces after the treatment is stopped.

  Glucocorticoids administered topically are most commonly prescribed in the initial treatment of psoriasis, and exert beneficial anti-inflammatory, antimitotic and antipruritic effects.

  Raw coal tar is a complex mixture of thousands of hydrocarbon compounds. Its therapeutic effect is linked to the inhibition of enzymes and to antimitotic properties. Although effective, this treatment is, by its odor, unpleasant to use for the patient and can induce skin cancers.

  Phototherapy and photo-chemotherapy based on the administration of 25 methoxsalen, the active photosensitizing ingredient, are only temporarily effective. Treatment should be repeated and offers palliative, but not curative, therapy. In addition, these treatments have long-term side effects, including immunologic alterations and an increased risk of carcinogenesis.

  Methotrexate is the most commonly used systemic cytotoxic agent for severe forms of psoriasis extending over a large area of the body. There are many contraindications for this treatment and stopping treatment may be accompanied by worsening of symptoms.

  Hydroxyurea, etretinate, cyclosporine, and AZT are also the systemic drugs used to fight psoriasis but all have serious side effects.

  To date, no treatment allows a lasting remission of this pathology without causing significant side effects, because psoriasis is a complex pathology of multifactorial origin. Understanding the pathophysiological mechanism leading to the psoriatic phenotype therefore remains an important challenge in dermatological medical treatment. Indeed, many aspects of the disease remain to be elucidated, such as the heterogeneous response to certain treatments, of patients with similar clinical signs.

  The nervous system is a complex set of many processes and 15 controls. Most of the activity of the nervous system is initiated by sensory receptors such as visual receptors, auditory receptors, tactile receptors on the surface of the skin or other receptors. The sensory system transmits information following actions such as touch, pressure or vibration to the brain from receptors present on the entire surface of the skin. This information enters the central nervous system through the peripheral nerves and is immediately led to many sensory areas such as in the spine, the medulla, the midbrain, the cerebral cortex, the thalamus.

  In view of the knowledge of the process of transmission of somatic sensations, nothing allows a person skilled in the art to deduce any involvement of the sensitive skin nerves in the physiological disturbance leading to the psoriatic phenotype.

  Analysis of gene expression in the skin of psoriatic patients 30 constitutes a way to better understand the pathophysiological mechanism of this disease (Bowcock AM, Shannon W, Du F, et al., Hum Mol Genet (2001) 10 (17 ): 1793-805; Oestreicher JL, Walters IB, Kikuchi T, et ai., Pharmacogenomics J (2001) 1 (4): 272-87).

  The technology of cDNA filters ("arrays") (NGuyen C, Rocha D, Granjeaud S, et ai., Genomics (1995)) is one of the technologies allowing to analyze simultaneously and quickly the expression of several hundred mRNAs from a skin biopsy taken from the patient, as opposed to other heavier technologies to implement, such as SAGE ("Serial Analysis of Gene Expression") (Velculescu VE, Zhang L, Vogelstein B, Kinzler KW, Science (1995 Oct) 20; 270 (5235): 484-7), or the Differential Display (Liang P, Pardee AB, Science (1992) 257: 967971; Zhang L, et ai., Science: (1997) 276: 1268-1272).

  The Applicant has identified a new marker gene for psoriasis.

  The subject of the present invention is a probe relating to the DPYSL3 gene for the characterization of a biological sample, and also a new tool for characterizing a compound intended for the treatment of psoriasis, as well as a new research tool.

  In particular, the invention relates to the use of a probe relating, respectively, to the DPYSL3 gene for the characterization of a biological sample.

  According to the present invention, a biological sample corresponds to any sample or sample of living organism, preferably a mammal, in particular a human organism, in an amount sufficient to be characterized.

  Mention may be made, as a biological sample, by way of nonlimiting example, of a sample of skin, scalp, mucosa, or cell.

  According to the present invention, the characterization of a biological sample consists in measuring the level of expression of a gene of interest, that is to say more precisely the quantity of messenger RNA or protein corresponding to this gene which is present in the biological sample.

  According to the present invention, the term “probe relating to a gene” means a polynucleotide probe or a polypeptide probe.

  In the case of a polynucleotide probe, it is a single or double-stranded oligo- or polynucleotide, of RNA or DNA, the sequence of which is complementary to a target sequence corresponding to part or all of said gene and which can range from 10 to conventionally 500 base pairs and whose sequence 5 is complementary to the target sequence by at least 80% and preferably by at least 90% (percentage of nucleic acid bases paired between two sequences, see the calculation methods proposed by Atschul et al. J. Molec. Biol. (1990), 215: 403).

  The polynucleotide probes according to the invention may be oligoor polynucleotides comprising one or more nucleotides modified by substitution, deletion or insertion, these modifications will be such that the sequence of the probe will allow it to specifically recognize the target sequence fragment.

  The polynucleotide probes may also have a modified backbone giving it, for example, better stability.

  For example, the phosphodiester bonds of the natural RNA strands can be modified to include at least one nitrogen or sulfur atom.

  The term “analog of a polynucleotide probe” is intended to mean an oligo- or polynucleotide whose phosphodiester bonds are replaced by peptide type sequences (peptide nucleic acids).

  In addition, the polynucleotide probes or their analogs according to the invention can comprise bases other than the 4 conventional bases.

  The polynucleotide probes or their analogs according to the invention can be synthesized according to numerous synthetic methods in vivo or in vitro, manually or automatically.

  The in vitro synthesis methods can be chemical or enzymatic.

  For example, a single-stranded cRNA probe may be obtained by in vitro transcription of a template of DNA sequence of interest serving as a template, using an RNA polymerase (for example T3, T7 or SP6 RNA polymerase).

  A single-stranded cDNA probe can be generated by reverse transcription of a 5 mRNA of interest in the presence of a reverse transcriptase (for example MMLV (Moloney Murine Leukemia Virus) Reverse Transcriptase isolated from Escherichia Coli).

  Many methods of in vivo synthesis of double stranded RNA are described in the literature, they can be carried out in various cell types of bacteria or higher organisms. Reference may also be made to the synthesis methods described in patent applications WO01 / 36646 and WO01 / 75164. These double stranded RNAs can then be denatured to serve as a single stranded polynucleotide.

  Regarding its environment, the polynucleotide probe can be or be part of a plasmid, a viral genome or another type of vector. It can, in other cases, be part of the genome of a cell, or else of a cell genetically modified to contain this probe in its genome. It can also be an isolated molecule.

  As regards the regions framing this probe, it is preferably under the control of regulatory sequences. If the probe is inserted into a vector, said vector preferably comprises all the sequences necessary for the transcription and optionally the translation of the probe. This probe can also be surrounded by flanking regions allowing a step of homologous recombination with another polynucleotide fragment, possibly leading to the insertion of the probe of the invention in the genomic DNA of a target cell.

  The polypeptide probes according to the invention are polypeptides capable of specifically binding with messenger RNA or with the protein encoded by the gene of interest.

  They may, for example, be mono- or polyclonal antibodies, or their biologically active fragment capable of recognizing the protein encoded by the gene of interest. These antibodies can be labeled, for example immunoconjugated with enzymes or labeled using fluorescent compounds, biotin or even radiolabelled.

  The polypeptide probes can be homologous polypeptides, variants or a modified form as well as active biological fragments derived from these polypeptides.

  By homologous polypeptides, is meant polypeptides whose amino acid sequences have at least 80%, and preferably 90% of amino acids in common.

  The term “variant polypeptide” is intended to denote a polypeptide which is mutated or which corresponds to a polymorphism which may exist, in particular in humans and which may exhibit truncation, substitution, deletion and / or addition of at least one amino acid relative to to the sequence of the normal wild-type polypeptide.

  By modified polypeptide is meant a polypeptide obtained by genetic recombination or by chemical synthesis, having a modification with respect to the normal wild-type sequence. These modifications may in particular relate to the pre-, pro- or mature domains of the polypeptides, to the amino acids at the origin of a spectrum specificity or of activity efficiency, or at the origin of the conformation. structural, load or hydrophobicity, and the multimerization and membrane insertion capacity of the polypeptides. It will thus be possible to create polypeptides of equivalent, narrower or wider activity. The modifications may also relate to the sequences involved in the processing, transport and addressing of the polypeptides.

  The term “biologically active fragment of a polypeptide” is intended to denote a polypeptide fragment having conserved at least one activity of the polypeptide from which it is derived.

  A comparative study of gene expression in psoriatic skin compared to healthy skin, enabled the Applicant to identify a gene, 5 designated DPYSL3 (Dihydropyrimidinase-like 3) or hULIP (unc-33-like phosphoprotein) or Collapsin response mediator protein 4, Genbank reference (NCBI): NM_001387.1, whose transcriptional activity is induced in diseased skin.

  This DPYSL3 gene is part of a family of TUC proteins, homologs to unc33 of C. Elegans, involved in neuronal growth (Quinn CC et al. J Neurobiol. (1999 Oct); 41 (1): 158-64; Nacher J et al. J Comp Neurol (2000 Sep) 4; 424 (4): 628-39; Byk T et al. J Neurosci. (1996 Jan) 15; 16 (2): 688-701).

  The DPYSL3 gene is also involved in neuronal differentiation and its expression is induced at the transcriptional level by retinoic acid (Gaetano C et al. J Biol Chem. (1997 May) 2; 272 (18): 12195-201).

  In particular, the present invention relates to the use of a polynucleotide or polypeptide probe relating to the DPYSL3 gene as defined above for the identification of a compound intended for the treatment of psoriasis.

  In a particular embodiment, the polynucleotide or polypeptide probe will be used in the method described below.

  The invention also relates to a method for identifying a compound intended for the treatment of psoriasis comprising the following steps: a) preparation of at least two biological samples; b) bringing one of the samples into contact with one or more compounds to be tested; c) measurement of the quantity of messenger RNA or of the protein corresponding to the DPYSL3 gene in the biological samples; d) selection of said compounds for which an inhibition of the transcription of the messenger RNAs of the DPYSL3 gene or of the expression of the corresponding protein is measured in the sample treated in step b).

  By inhibiting the transcription of a DPYSL3 gene or the expression of the protein is meant a reduction in the quantity of messenger RNA or of the protein corresponding to said gene in a test sample.

  In another embodiment, the present invention relates to a research tool comprising a probe relating to the DPYSL3 gene.

  The research tool may also allow analysis of the effects of certain treatments on the expression of these psoriasis marker genes, or analysis of the mutation in the sequence of these genes in individuals suffering from psoriasis.

  For example, this search tool could be such that the probe or probes that it comprises, are brought into contact with the corresponding target sequence (s) deposited on a support such as a filter in nylon.

  The probe can be used in a hybridization test (for example a mismatch detection test), sequencing, microsequencing.

  According to other research tools envisaged by the present invention, the probe according to the invention may be associated with another detectable probe, the nature of which may preferably be fluorescent, radioactive or enzymatic.

  This characteristic can make it possible, among other things, to follow the location of the probe, from the extracellular medium to the cell, or from the cytoplasm to the nucleus, or else to specify its interaction with DNA, or RNA or proteins.

  Those skilled in the art will know which detectable probe is best suited as a function of the characteristic that they want to be able to follow.

  The discovery of the overexpression of the DPYSL3 gene in psoriatic skin makes it possible on the one hand to diagnose psoriasis, and on the other hand, to develop new therapeutics based on the inhibition of the expression and / or the function of DPYSL3 to treat psoriasis by limiting the neural component that characterizes it.

  In a particularly preferable aspect, the present invention provides a method for characterizing skin samples to determine predisposition to psoriasis.

  The Applicant has demonstrated that the expression of the DPYSL3 gene is induced in lesional psoriatic skin with a plaque of psoriasis, compared to healthy skin (average expression measured in 13 psoriatic subjects and 10 healthy subjects).

  The results obtained are presented in Table 1.

  Measuring the expression of DPYSL3 makes it possible to characterize lesional psoriatic skin independently of the type and location of the psoriasis plaque (Tables 2 and 3). Table 2 shows the expression of DPYSL3 relative to an average expression in healthy subjects, in patients with predominantly trunk and asymmetric plaques. Table 3 represents the expression of DPYSL3 relative to an average expression in healthy subjects, in patients presenting mainly symmetrical plaques.

  In addition, apart from the characterization of a skin having a plaque of psoriasis compared to healthy skin, the discovery of this new marker of psoriasis also makes it possible to discriminate a skin of psoriatic patient not lesional (clinically healthy) but already committed towards the psoriatic process, of non-lesional skin having the real characteristics of healthy skin.

  The Applicant has surprisingly discovered that certain non-lesional skins also overexpress the DPYSL3 gene. On the basis of the expression of this gene, the diagnosis of psoriasis is achievable very early since the expression of the DPYSL3 gene makes it possible to differentiate at the molecular level from non-lesional skin already affected, whereas the clinical signs do not allow it. The results obtained are presented in Table 4.

  Thus, the invention also relates to a method for diagnosing psoriasis or a predisposition to psoriasis comprising a step of measuring the overexpression in a biological sample of the DPYSL3 gene using a probe relating to the DPYSL3 gene.

  By overexpression of a gene in a biological sample is meant a higher expression of the messenger RNA or of the protein corresponding to this gene in this sample compared to a healthy reference sample.

  Furthermore, the invention also relates to a diagnostic kit comprising a probe relating to the DPYSL3 gene.

  The observations described above also indicate that DPYSL3 is a therapeutic target for the development of new therapies aimed at treating chronic vulgar plaque psoriasis, whatever the predominant type of plaque in the patient, and the location of the psoriasis plaque on the body.

  Thus, another object of the present invention relates to the use of a polynucleotide probe or one of its analogues, complementary, to the DPYSL3 gene to inhibit the expression of the DPYSL3 gene.

  In particular, the polynucleotide probe may be an antisense RNA or a siRNA which has the role of inhibiting the expression of a specific gene (Fire A., Trends in Genetic (1999); 15: 358-363).

  Finally, the invention also relates to the use of a polynucleotide probe or one of its analogs, complementary to the DPYSL3 gene for the manufacture of a pharmaceutical composition intended for the treatment of psoriasis.

  EXAMPLE 1 - MEASUREMENT OF GENE EXPRESSION IN HEALTHY SKIN

AND IN PSORIASIC SKIN

  A clinical study carried out in the presence of healthy volunteers and patients suffering from chronic vulgar plaque psoriasis has made it possible to demonstrate the involvement of the DPYSL3 gene in psoriasis. Skin biopsies are taken from healthy volunteers, as well as from psoriasis plaques and from non-lesional areas that appear clinically healthy, from patients with psoriasis. The presence or absence of psoriasis on the area of biopsied skin, as well as the severity of the psoriasis plaque, are determined by the evaluation of local clinical parameters (erythema, scaling and plaque elevation scores). psoriasis).

  Analysis of gene expression is then performed from each individual biopsy. The comparison of the gene profiles corresponding to healthy skin and psoriatic non-lesional and lesional skin, makes it possible to identify genes whose expression is induced in the disease.

  The determination of the gene profiles is based on the hybridization of a complex single-stranded cDNA probe (generated by the reverse transcription of the mRNAs from each skin biopsy) on cDNA fragments of interest, which are deposited on a support such as a nylon filter. The hybridization signals obtained are proportional to the quantity of each labeled cDNA in the probe and reflect the level of expression of each mRNA in the analyzed skin sample (Nguyen C et al. Genomics (1995 Sep) 1 ; 29 (1): 207-1 6).

  Filters developed by the Applicant, specific to dermatology have been developed. These filters consist of 474 cDNAs involved in the physiological processes of human skin. In parallel, commercial filters with 4200 human cDNAs (Invitrogen GF21 1) were used. These cDNA filters will make it possible to determine the expression of genes of interest in healthy skin as well as in non-lesional and lesional skin of patients suffering from chronic vulgar plaque psoriasis.

  Method The measurement of gene expression in healthy skin and in psoriatic skin is carried out using the technology of cDNA filters ("<arrays") on nylon support.

  The principle of this technology is based on the hybridization of a single-stranded cDNA probe radiolabelled on target cDNA fragments deposited at high density on nylon filters (Nguyen C et al. Genomics (1995 Sep) 1; 29 (1): 207-16). In this study, nylon filters (GF21 1) sold by the company Invitrogen on which 4200 identified human cDNAs are deposited, as well as filters dedicated to dermatology with 474 human cDNAs, developed by the Applicant, are used. The radiolabelled cDNA probes are generated by retrotranscription of the total RNAs (Invitrogen protocol), isolated from various biopsies taken from 10 healthy volunteers and 13 subjects suffering from chronic plaques of common psoriasis (RNEasy protocol, Qiagen). The hybridization signals obtained are proportional to the quantity of each labeled cDNA present in the probe, which has hybridized to the cDNA which is complementary to it on the filter and thus reflect the transcriptional activity of the mRNAs in the biopsies analyzed.

  Analysis, normalization of language expression results and comparison of gene profiles between healthy skin and psoriatic skin Hybridization signals are measured by phospholuminescence, then quantified using Imagen image analysis software ( Biodiscovery).

  In order to discriminate the specific hybridization signals of the genes studied, the background noise linked to non-specific hybridization is measured on each filter on virgin areas of cDNA deposition (GF211 filters), or within a surrounding crown. each spot (dedicated filters). After transforming the 30 data into log, a detection threshold making it possible to discriminate a measurement pertaining to a real signal or noise, is automatically determined for each filter using the method described previously by Fogel et al., 2002.

  In order to compare the gene expression results between the different biopsies analyzed, the hybridization signals are normalized by the median of the set of signals obtained for each biopsy (filters GF21 1), or by s the expression of an exogenous messenger RNA, serving as a reference, the expression of which is invariant between the samples analyzed. This exogenous transcript is added in constant quantity to the total RNA preparations from the different samples, before synthesis of the radiolabelled cDNA probe. The target sequence of this exogenous transcript is deposited on each filter.

  For each gene, an average reference expression is determined on all the biopsies of healthy subjects, then subtracted from the expression obtained in each biopsy of non-lesional and lesional psoriatic skin (values in log). The ratio between the expression of each gene in psoriatic skin compared to healthy skin is then obtained by taking the base 10 exponential of the value calculated previously (Tables 1 to 4).

  The results obtained make it possible to demonstrate the overexpression of the DPYSL3 gene in lesional human skin having a plaque of psoriasis compared to healthy human skin (Table 1).

  The results of Tables 2 and 3 indicate that this overexpression is observed whatever the predominant type of plaques expressed in the patient (symmetrical or truncated) and also independently of the location of the psoriasis plaques. The abbreviations mentioned in these tables represent the location of the biopsies taken from the body for each psoriatic subject (SP) and have the following meaning: JG: left leg, JD: 25 right leg, BD: right arm, BG: left arm, T : trunk. The results in Table 4 show that the expression of this gene is

  also induced in non-lesional psoriatic skin. The abbreviations have the same meaning as before.

  EXAMPLE 2 - MEASUREMENTS OF LOCAL CLINICAL PARAMETERS RELATED TO THE PSORIASIS PLATE: ERYTHHEM SCORES. DEQUAMATION AND PLATE RAISING The various local clinical scores used to define the presence or absence of psoriasis on the biopsied skin area, as well as the severity of the psoriasis plaque, are the erythema, flaking and plate elevation. These scores are conventionally measured by the following classifications: The measurement of erythema is done using the following classification: 0 = none (no erythema) 1 = slight (slight redness present) 2 = moderate (redness easily detectable ) 15 3 = severe (intense redness) 4 = very severe (very intense redness) The measurement of scaling is done using the following classification: 0 = none (no scaling) l = mild (dander detected, only one layer of desquamation) 2 = moderate (dander of intermediate degree between light and severe) 3 = severe (several layers of dander) 4 = very severe (several layers of dander thick) The measurement of the elevation of the plate is done using the following classification: 0 = none (no elevation in thickness) 1 = slight (slight elevation detectable by touch) 2 = moderate (moderate thickness) 3 = severe (strong thickening) 4 = very severe ( very strong thickening) This study shows that the local clinical parameters obtained with psoriatic non-lesional skin are not different from those obtained for healthy skin. They therefore do not make it possible to differentiate psoriatic non-lesional skin from healthy skin.

  On the other hand, the results of table 4 made it possible to demonstrate at the molecular level, an overexpression of the DPYSL3 gene in certain non-lesional psoriatic skin.

  Measuring the expression of the DPYSL3 gene therefore makes it possible to carry out a very early diagnosis of psoriasis, since the expression of these genes makes it possible to differentiate at the molecular level non-lesional skin already affected, while the clinical signs do not allow it. not.

Claims (6)

  1. Use of a polynucleotide probe, said probe having a sequence of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 001387.1) , to characterize a biological sample by measuring the level of expression of the DPYSL3 gene.   2. Use of a polynucleotide probe, said probe having a sequence 10 of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 001387.1) , for the identification of a compound intended for the treatment of psoriasis.   3. A method of identifying a compound intended for the treatment of psoriasis comprising the following steps a) preparation of at least two biological samples b) bringing one of the samples into contact with one or more compounds to be tested; c) measuring the quantity of messenger RNA corresponding to the DPYSL3 gene in biological samples using a polynucleotide probe, said probe having a sequence of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 25 001387.1); d) selection of said compounds for which an inhibition of the transcription of the messenger RNAs of the DPYSL3 gene is measured in the sample treated in step b).   4. Research tool comprising a polynucleotide probe, said probe having a sequence of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 001387.1) .   5. A method of diagnosing psoriasis or a predisposition to psoriasis comprising a step of measuring the overexpression in a biological sample of the DPYSL3 gene by bringing a polynucleotide probe into contact with the target sequences isolated from said biological sample, said probe having a sequence of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 001387.1).   6. diagnostic kit comprising a polynucleotide probe, said probe having a sequence of 10 to 500 base pairs and being at least 80% complementary with a target sequence corresponding to all or part of the DPYSL3 gene (accession number NM 001387.1) .