| First Author | Liu X | Year | 2012 |
| Journal | J Immunol | Volume | 189 |
| Issue | 2 | Pages | 669-78 |
| PubMed ID | 22711892 | Mgi Jnum | J:189797 |
| Mgi Id | MGI:5447003 | Doi | 10.4049/jimmunol.1200607 |
| Citation | Liu X, et al. (2012) The T cell response to IL-10 alters cellular dynamics and paradoxically promotes central nervous system autoimmunity. J Immunol 189(2):669-78 |
| abstractText | IL-10 is a critical anti-inflammatory cytokine, the deficiency of which leads to spontaneous autoimmunity. However, therapeutically administered or ectopically expressed IL-10 can either suppress or promote disease. Distinct lineage-specific activities may explain the contradictory effects of IL-10. To dissect the T cell-specific response to IL-10 during organ-specific autoimmunity, we generated mice with a selective deletion of IL-10Ralpha in T cells and analyzed its effects in an autoimmune model, experimental allergic encephalomyelitis (EAE). Surprisingly, the T cell response to IL-10 increased EAE severity. This did not result from altered T cell functional potential; T cell cytokine profile was preserved. IL-10 also diminished the proliferation of T cells in situ within the target organ, an effect that would be expected to restrain disease. However, IL-10 acted cell autonomously to sustain the autoreactive T cells essential for immunopathogenesis, promoting their accumulation and distorting the regulatory and effector T cell balance. Indeed, in chimeric mice and after adoptive transfer, wild type T cells showed a competitive advantage over cells deficient in IL-10Ralpha. Therefore, T cell specific actions of IL-10 can support autoimmune inflammation, and this appears to result from an overall increase in the long term fitness of pathologic T cells. Lineage-restricted, disease-promoting activities of IL-10 should be considered in the therapeutic manipulation of the IL-10 pathway. |
