CN105693850A - Key chemokine receptor and ligand promoting situation that poultry T cells migrate to target organ and application of receptor and ligand - Google Patents
Key chemokine receptor and ligand promoting situation that poultry T cells migrate to target organ and application of receptor and ligand Download PDFInfo
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- CN105693850A CN105693850A CN201610104065.XA CN201610104065A CN105693850A CN 105693850 A CN105693850 A CN 105693850A CN 201610104065 A CN201610104065 A CN 201610104065A CN 105693850 A CN105693850 A CN 105693850A
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Abstract
The invention provides a key chemokine receptor and ligand promoting the situation that poultry T cells migrate to a target organ and application of the receptor and the ligand. The receptor mainly comprises CCR4, CCR5, CCR6, CCR7 and CXCR4 and the ligand mainly comprises CCL17/CCL22, CCL3/CCL4, CCL20, CCL19/CCL21 and CXCL12. Gene expression changes of the chemokine receptor and the ligand in a poultry bursa fabricius organ infected by infectious bursal disease viruses are detected through quantitative PCR and a transcriptome sequencing technology, in the result, it is found that the gene expression quantity of the chemokine receptor CCR4, CCR5, CCR6, CCR7 and CXCR4 and the ligand of bursa fabricius tissue T cells in an infectious bursal disease virus (IBDV) infected group remarkably changes, and the gene expression quantity changes play an important role in T cell migration.
Description
Technical field
The present invention relates to biomedicine field, be specifically related to promote the application of crucial chemokine receptors that poultry T cell migrates to target organ and part and receptor and part thereof。
Background technology
Infectious bursal disease is acute, the high degree in contact sexually transmitted disease that are caused chicken by infections chicken cloacal bursa virus (Infectiousbursaldiseasevirus, IBDV)。IBDV infects the immune system that can pass through number of ways destruction chicken, causes immunosuppressant, makes the easy secondary superinfection of chicken cause death。After IBDV infects, another feature of fabricius bursa is exactly a large amount of external source CD4+ and CD8+T cell migration to fabricius bursa, promote macrophages secrete proinflammatory factor (such as IL-1 β, IL-6, CXCi2 and IFN-γ etc.), delay the reparation of lymph follicle, cause immunosuppressant。IL-6 and IFN-γ along with high level expression, monocytes/macrophages is activated, cause so-called " cytokine storm ", such as proinflammatory factor (such as IL-1 β, IL-6 and iNOS etc.) and chemotactic factor (such as IL-8, MIP-α and NO etc.), cause the acute inflammation of fabricius bursa to damage。
After infecting, a large amount of CD4+T and CD8+T cell migration are to fabricius bursa for IBDV, and in animal body, in target organ, the change of CD4+T and CD8+T cell quantity and ratio just can affect surviving of animal。Therefore, the research carrying out the IBDV target organ T cell chemokine receptors replicated in poultry body contributes to illustrating the body anti-ibd V molecular mechanism infected
Up to the present, the T cell chemokine gene people having identified out has 42, and mice has 36, and chemokine receptors people and mice have 19, the identified chemotactic factor out of chicken and acceptor gene respectively 23 and 14, the T lymphocyte of chicken can express 10 chemokine receptors。T.Annamalai etc. confirm by comparing CD4+ and CD8+T cellular chemokine receptors in peripheral blood, fabricius bursa, cecal tonsil, spleen and thymus (CCR2, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CXCR4, CXCR5 and CX3CR1) mrna expression level, CCR5 and the CXCR5 of CD4+T cells express high levels in fabricius bursa, cecal tonsil source CD8+T cell except CCR9 and CX3CR1, other chemokine receptors of high level expression；It addition, ConA stimulates can increase CD4+ and CD8+T cellular chemokine receptors expression in various degree。
T cell associated chemokine and the generation of receptors on lymphocytes, migration, break up, go back to the nest and immunne response and regulate in play an important role。After the research such as T.Annamalai finds lumbar injection LPS24h, splenocyte CCR7mRNA expression decreases beyond 100 times, fabricius bursa cell CXCR5mRNA reduces about 5 times, and give chicken immune coccidiosis live vaccine after 10 days, in cecal tonsil, CCR7mRNA expression raises 15 times, CXCR5mRNA expression raises 12 times, and CCR7 and CXCR5mRNA level depends on immune organ and the immune organ inflammatory reaction degree of chicken。SamanthaR.Slight etc. are found by humans and animals tubercule bacillus scale-model investigation, pulmonary Mycobacterium has CXCR5+T cell aggregation, proinflammatory factor can be produced by activating macrophage, Cxcr5 deficient mice more susceptible tubercule bacillus, CD4+CXCR5+T cell plays a significant role in anti-mycobacterium tuberculosis immunity, has application prospect in Vaccinum Calmette-Guerini design with treatment。Lymphoma caused after infecting for MDV is formed closely related with the viral IL-8 of chemotactic factor, and it can pass through to attract B cell and CD4+CD25+T cell aggregation to form lymphoma to diseased region。
In sum, the T cell moved in fabricius bursa tissue is played a great role in " cytokine storm " caused by IBDV, and key problem is T cell, and to move to the molecular mechanism of fabricius bursa not clear。Understand that in the fabricius bursa of IBDV infection front and back, T cell chemotactic factor and expression of receptor situation are to explaining that T cell moves to fabricius bursa and organizes this phenomenon most important。
Summary of the invention
In order to solve the deficiencies in the prior art, the invention provides the application promoting crucial chemokine receptors that poultry T cell migrates to target organ and part and receptor and part thereof。
The technical scheme is that the crucial chemokine receptors and the part thereof that promote that poultry T cell migrates to target organ, described receptor is the part of CCR4, CCR5, CCR6, CCR7 and CXCR4 and prefabricated coupling is CCL17 or CCL22, CCL3 or CCL4, CCL20, CCL19 or CCL21 and CXCL12。
Further improvement of the present invention includes:
Described target organ is fabricius bursa。
Described poultry includes chicken, duck, goose。
Another object of the present invention is to the application providing a kind of above-mentioned receptor and part thereof in poultry T cell migrates to target organ。
Described application, utilizes described receptor and part to carry out directed attraction T cell and migrates the infection preventing pathogenic microorganism。
Described application, described pathogenic microorganism is infectious bursal disease virus。
Invention further provides the application in preparation treatment or prevention poultry cause pathogeny imcrobe infection medicine of a kind of above-mentioned receptor and part thereof。
The present invention is to provide the key factor promoting that poultry T cell migrates to target organ, mainly utilizes IBDV to infect SPF chicken model searching T cell and moves to the key factor of fabricius bursa organ。
After infectious bursal disease virus IBDV infects SPF chicken, one significant feature is exactly that T cell moves to fabricius bursa tissue in a large number, after artificial challenge's model is set up, by the change of T cell chemokine receptors (CCR2, CCR4, CCR5, CCR6, CCR7, CCR8, CCR9, CXCR4, CXCR5, CX3CR1 and XCR1 etc.) and ligand gene expression thereof in the Ji Shucedingfashi lens capsule tissues such as RT-PCR and transcript profile order-checking。
It was found that the 1st day and the 3rd day T cell chemokine receptors CCR4, CCR5, CCR6, CCR7 and CXCR4 gene expression amount significantly raise after viral infection, corresponding part CCL17, CCL4, CCL20, CCL19 gene expression amount also significantly raises；And part CXCL12 the 1st day gene expression amount after infection raises, after infection, the 3rd day expression declines。
Accompanying drawing explanation
Fig. 1 is CCR4/CCR5/CCR6/CCR7/CXCR4 gene expression in fabricius bursa tissue after infecting 1 day。
Fig. 2 is CCR4/CCR5/CCR6/CCR7/CXCR4 gene expression in fabricius bursa tissue after infecting 3 days。
Fig. 3 is the VP2 gene content of virus IBDV in embodiment 2。
Detailed description of the invention
Below in conjunction with specific embodiment, the present invention is elaborated。
The key factor research that embodiment 1 poultry T cell migrates
EXPERIMENTAL DESIGN: 24 21 age in days SPF chickens are randomly divided into 2 groups, respectively infection group and viral infection group (9) and normal healthy controls group (15), every chicken eye dripping, Di Bifashi lens capsule tissue virus dilution liquid 0.2ml, within after counteracting toxic substances 1 day and 3 days, taking fabricius bursa, liquid nitrogen flash freezer is placed on-80 DEG C of Refrigerator stores。The pathological material of disease preserved carries out RNA extraction, reverse transcription, then carries out quantitative PCR and transcript profile order-checking。T cell chemokine receptors gene expression results is shown in Fig. 1 and Fig. 2。
Quantitative PCR result shows, after viral infection the 1st day, and in infection group and viral infection group fabricius bursa tissue, CCR4/CCR5/CCR6/CCR7/CXCR4 gene content significantly improves, and is respectively higher than normal healthy controls group about 70,25,60,20 and 3 times。After this illustrates that IBDV infects SPF chicken, in fabricius bursa, CCR4/CCR5/CCR6/CCR7/CXCR4 significantly changes, it is possible to participate in the T cell directional migration process to fabricius bursa。
After viral infection the 3rd day, in infection group and viral infection group fabricius bursa tissue, CCR4/5/6/7 gene content was still higher than normal healthy controls group, simply than content reduction in the 1st day after infecting；But CXCR4 gene expression amount reduces than normal healthy controls group, about reduce by 8 times。
2. transcript profile sequencing result
Transcript profile sequencing result shows, T cell chemokine receptors CCR4/CCR5/CCR6/CCR7/CXCR4 variation tendency is consistent with reverse transcription (RT-PCR) result；Corresponding part CCL17, CCL4, CCL20, CCL19 gene expression amount all significantly raises for the 1st day and the 3rd day after viral infection；And part CXCL12 the 1st day gene expression amount after infection raises, after infection, the 3rd day expression declines。
After conclusion: IBDV infects, the change of T cell chemokine receptors CCR4/CCR5/CCR6/CCR7/CXCR4 and part CCL17, CCL4, CCL20, CCL19, CXCL12 gene expression content thereof describes them and plays a great role in fabricius bursa tissue at T cell directional migration。So, CCR4/CCR5/CCR6/CCR7/CXCR4 and part CCL17, CCL4, CCL20, CCL19, CXCL12 as the potential key factor being applied to poultry T cell directional migration, also can provide experimental data and theoretical basis for them simultaneously at T cell directional migration。
Subordinate list chemokine receptors primer
Embodiment 2 chemokine receptor CCR 5 and the application in IBDV infects of the CXCR4 antagonist
EXPERIMENTAL DESIGN: 24 21 age in days SPF chickens are randomly divided into 4 groups, respectively infection group and viral infection group, normal healthy controls group, CCR5 antagonist Maraviroc group and CXCR4 antagonist AMD3100 group, often 6 chickens of group。Counteracting toxic substances sampling eye dripping, every chicken IFN-γ V virus liquid 0.2ml of collunarium mode, antagonist a few days ago feeds in counteracting toxic substances, the dosage of Maraviroc and AMD3100 calculates according to 0.5 and 1mg/kg body weight respectively, within after viral infection the 3rd day, takes fabricius bursa, and liquid nitrogen flash freezer is placed on-80 DEG C of Refrigerator stores。The pathological material of disease preserved carries out RNA extraction, reverse transcription, then carries out the VP2 gene content of quantitative PCR detection virus IBDV。
As Fig. 3 result shows, after viral infection the 3rd day, in infection group and viral infection group, VP2 gene content sharply raises, and the rising of VP2 fund content becomes apparent from antagonist group, in Maraviroc and AMD3100 two groups, VP2 content is 3 times and 2 times of infection group and viral infection group content respectively, illustrates that antagonist papova content raises。
Chemokine receptor expression research in embodiment 3 Muscovy duck body
Duckling 10 from about certain duck field random choose 30 age in days of Xinxiang, wins thymus and spleen, and liquid nitrogen flash freezer is placed on-80 DEG C of Refrigerator stores。The pathological material of disease preserved carries out RNA extraction, reverse transcription, then carries out quantitative PCR detection chemokine receptor expression situation。
Result shows, duckling thymus and spleen can effective expression chemokine receptors CCR4/CCR5/CCR6/CCR7/CXCR4, a little higher than spleen of thymus gene expression amount。
The ultimate principle of the present invention and principal character and advantages of the present invention have more than been shown and described。Skilled person will appreciate that of the industry; the present invention is not restricted to the described embodiments; described in above-described embodiment and description is that principles of the invention is described; without departing from the spirit and scope of the present invention; the present invention also has various changes and modifications, and these changes and improvements both fall within the claimed scope of the invention。Claimed scope is defined by appending claims and equivalent thereof。
Claims (7)
1. promote crucial chemokine receptors and part thereof that poultry T cell migrates to target organ, it is characterized in that, described receptor is the part of CCR4, CCR5, CCR6, CCR7 and CXCR4 and prefabricated coupling is CCL17 or CCL22, CCL3 or CCL4, CCL20, CCL19 or CCL21 and CXCL12。
2. the crucial chemokine receptors promoting poultry T cell to migrate to target organ according to claim 1 and part thereof, it is characterised in that described target organ is fabricius bursa。
3. the crucial chemokine receptors promoting poultry T cell to migrate to target organ according to claim 1 and part thereof, it is characterised in that described poultry includes chicken, duck, goose。
4. a receptor as claimed in claim 1 and part application in poultry T cell migrates to target organ thereof。
5. application according to claim 4, it is characterised in that utilize described receptor and part to carry out directed attraction T cell and migrate the infection preventing pathogenic microorganism。
6. application according to claim 5, it is characterised in that described pathogenic microorganism is infectious bursal disease virus。
7. a receptor as claimed in claim 1 and part application in preparation treatment or prevention poultry cause pathogeny imcrobe infection medicine thereof。
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114392347A (en) * | 2022-01-21 | 2022-04-26 | 河南科技学院 | Application of avian-derived chemokine CCL19 in preparation of antiviral product |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557487A (en) * | 2004-01-29 | 2004-12-29 | 郭占军 | Immunogenicity composition for preventing and treating diseases and its preparation |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1557487A (en) * | 2004-01-29 | 2004-12-29 | 郭占军 | Immunogenicity composition for preventing and treating diseases and its preparation |
Non-Patent Citations (2)
| Title |
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| JIXIN WANG等: "Genomic organization, annotation, and ligand-receptor inferences of chicken chemokines and chemokine receptor genes based on comparative genomics", 《BMC GENOMICS》 * |
| 周灵 等: "T细胞相关趋化因子及受体的研究进展", 《免疫学杂志》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114392347A (en) * | 2022-01-21 | 2022-04-26 | 河南科技学院 | Application of avian-derived chemokine CCL19 in preparation of antiviral product |
| CN114392347B (en) * | 2022-01-21 | 2023-06-23 | 河南科技学院 | Application of avian chemokine CCL19 in preparing antiviral product |
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Application publication date: 20160622 |