Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses.
<h4>Objective</h4>IL-22 is elevated in patients with inflammatory arthritis and correlates with disease activity. IL-22 deficient mice have reduced incidence of arthritis. Recombinant IL-22 restrains progression of arthritis via increase in IL-10 responses when administered prior to onse...
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093279&type=printable |
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| author | Shivali Justa Xiaoqun Zhou Sujata Sarkar |
| author_facet | Shivali Justa Xiaoqun Zhou Sujata Sarkar |
| author_sort | Shivali Justa |
| collection | DOAJ |
| description | <h4>Objective</h4>IL-22 is elevated in patients with inflammatory arthritis and correlates with disease activity. IL-22 deficient mice have reduced incidence of arthritis. Recombinant IL-22 restrains progression of arthritis via increase in IL-10 responses when administered prior to onset of arthritis. These findings imply a possible dual role of IL-22 in inflammatory arthritis depending on the phase of arthritis. Experiments outlined here were designed to elucidate the contribution of endogenous IL-22 before and after the onset of arthritis.<h4>Methods</h4>Collagen induced arthritis (CIA) was induced in DBA1 or IFN-γ deficient mice following immunization with collagen and complete Freund's adjuvant. Anti-IL-22 antibody or isotype control were administered prior to or after onset of arthritis and disease progression assessed by clinical scoring and histopathology. IL-22, IL-17 and IFN-γ responses were measured by ELISA and flowcytometry. Anti-collagen antibody responses were analyzed by ELISA. Expression of IL-22R1 in CD4+ cells was elucidated by flowcytometry and real time PCR.<h4>Results</h4>Collagen specific IL-22 responses were expanded during arthritis and IL-22 producing cells were discrete from IL-17 or IFN-γ producing cells. Neutralization of IL-22 after onset of arthritis resulted in significant increase in Th1 responses and significantly reduced severity of arthritis. CD4+ cells from arthritic mice showed increased surface expression of IL-22R1. In vitro, CD4+T cells cultured with antigen presenting cells in the presence or absence of IL-22 suppressed or induced IFN-γ, respectively. The protective effect of anti-IL-22 was reversed in IFN-γ deficient mice. Moreover, administration of anti-IL-22 prior to onset of arthritis augmented arthritis severity.<h4>Conclusion</h4>We show for the first time that IL-22 plays a dual role: protective prior to the onset of arthritis and pathogenic after onset of arthritis. The pathogenic effect of IL-22 is dependent on suppression of IFN-γ responses. IL-17 responses remained unchanged with the administration of anti-IL22 antibody. IL-22R1 is upregulated on CD4+T cells during arthritis and regulates IFN-γ in T cells. |
| format | Article |
| id | doaj-art-e7a7baad80f04bf7bb7c3347db746579 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e7a7baad80f04bf7bb7c3347db7465792025-08-20T03:01:32ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9327910.1371/journal.pone.0093279Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses.Shivali JustaXiaoqun ZhouSujata Sarkar<h4>Objective</h4>IL-22 is elevated in patients with inflammatory arthritis and correlates with disease activity. IL-22 deficient mice have reduced incidence of arthritis. Recombinant IL-22 restrains progression of arthritis via increase in IL-10 responses when administered prior to onset of arthritis. These findings imply a possible dual role of IL-22 in inflammatory arthritis depending on the phase of arthritis. Experiments outlined here were designed to elucidate the contribution of endogenous IL-22 before and after the onset of arthritis.<h4>Methods</h4>Collagen induced arthritis (CIA) was induced in DBA1 or IFN-γ deficient mice following immunization with collagen and complete Freund's adjuvant. Anti-IL-22 antibody or isotype control were administered prior to or after onset of arthritis and disease progression assessed by clinical scoring and histopathology. IL-22, IL-17 and IFN-γ responses were measured by ELISA and flowcytometry. Anti-collagen antibody responses were analyzed by ELISA. Expression of IL-22R1 in CD4+ cells was elucidated by flowcytometry and real time PCR.<h4>Results</h4>Collagen specific IL-22 responses were expanded during arthritis and IL-22 producing cells were discrete from IL-17 or IFN-γ producing cells. Neutralization of IL-22 after onset of arthritis resulted in significant increase in Th1 responses and significantly reduced severity of arthritis. CD4+ cells from arthritic mice showed increased surface expression of IL-22R1. In vitro, CD4+T cells cultured with antigen presenting cells in the presence or absence of IL-22 suppressed or induced IFN-γ, respectively. The protective effect of anti-IL-22 was reversed in IFN-γ deficient mice. Moreover, administration of anti-IL-22 prior to onset of arthritis augmented arthritis severity.<h4>Conclusion</h4>We show for the first time that IL-22 plays a dual role: protective prior to the onset of arthritis and pathogenic after onset of arthritis. The pathogenic effect of IL-22 is dependent on suppression of IFN-γ responses. IL-17 responses remained unchanged with the administration of anti-IL22 antibody. IL-22R1 is upregulated on CD4+T cells during arthritis and regulates IFN-γ in T cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093279&type=printable |
| spellingShingle | Shivali Justa Xiaoqun Zhou Sujata Sarkar Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. PLoS ONE |
| title | Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. |
| title_full | Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. |
| title_fullStr | Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. |
| title_full_unstemmed | Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. |
| title_short | Endogenous IL-22 plays a dual role in arthritis: regulation of established arthritis via IFN-γ responses. |
| title_sort | endogenous il 22 plays a dual role in arthritis regulation of established arthritis via ifn γ responses |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0093279&type=printable |
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