Regulation of T cells and cytokines by the interleukin-10 (IL-10)-family cytokines IL-19, IL-20, IL-22, IL-24 and IL-26.
The family of IL-10-related cytokines includes several human members, IL-19, IL-20, IL-22, IL-24 and IL-26, and a series of herpesviral and poxviral paralogs. Some of these cytokines share common receptor subunits. In this study, we investigated the effects of these cytokines on naive T cell differentiation, antigen-specific T cell suppression, survival ad expression of surface markers in comparison to IL-10 and cytomegalovirus (CMV)-IL-10. Human CD45RA(+) T cells were stimulated in the presence of IL-10-family cytokines in sequential 12-day cycles. After three to four cycles of stimulation, IL-10 and CMV-IL-10 led to increased IFN-gamma and IL-10 but decreased IL-4 and IL-13. Interestingly, long-term exposure of T cells to IL-19, IL-20 and IL-22 down-regulated IFN-gamma but up-regulated IL-4 and IL-13 in T cells and supported the polarization of naive T cells to Th2-like cells. In contrast, neutralization of endogenous IL-22 activity by IL-22-binding protein decreased IL-4, IL-13 and IFN-gamma synthesis. The antigen-specific suppressor activity of IL-10 and CMV-IL-10 was not observed for any of the other IL-10-family cytokines. These data demonstrate that IL-19, IL-20 and IL-22 may participate in T cell-mediated diseases by distinct regulation of T cell cytokine profiles.
Oral
Haluk B
HB
Department of Microbiology & Infectious Diseases, Immunology Unit, Uludag University School of Medicine, 16059 Bursa, Turkey. oralb@uludag.edu.tr
Kotenko
Sergei V
SV
Yilmaz
Mustafa
M
Mani
Orlando
O
Zumkehr
Judith
J
Blaser
Kurt
K
Akdis
Cezmi A
CA
Akdis
Mübeccel
M
D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D017493:Leukocyte Common Antigens / Q000096:biosynthesis / Q000276:immunology; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors; D014764:Viral Proteins / Q000276:immunology / Q000494:pharmacology*
C446339:CMV IL-10 protein, Cytomegalovirus; D016207:Cytokines; D014764:Viral Proteins; D017493:Leukocyte Common Antigens