IL-10 suppresses Th17 cells and promotes regulatory T cells in the CD4+ T cell population of rheumatoid arthritis patients.
Interleukin-17-producing CD4(+) T cells (Th17 cells) are the dominant pathogenic cellular component in autoimmune inflammatory diseases, including autoimmune arthritis. IL-10 promotes the generation of Foxp3(+) regulatory T cells via the IL-10 receptor signal. The objective of this study was to examine whether IL-10, which acts as an anti-inflammatory cytokine, has a suppressive effect on the activation of human Th17 cells. Expression of IL-17 and IL-10 was examined immunohistochemically in tissue obtained from rheumatoid arthritis patients. Human peripheral blood CD4(+) T cells were isolated and cultured under various stimulatory conditions. Th17 cells and regulatory T (Treg) cells were detected by flow cytometry. The gene expression of related cytokines and transcription factors were assessed by ELISA and RT-PCR. IL-17 was overexpressed in rheumatoid arthritis patients. IL-10 treatment significantly decreased the numbers of IL-17-producing and RORc-expressing cells among human CD4(+) T cells that had been activated in vitro by Th17-differentiating conditions in autoimmune arthritis patients. IL-10 induced Foxp3(+) regulatory T cells in the human CD4(+) T cell population. Our results demonstrate that IL-17 is overexpressed in autoimmune disease patients and that IL-10 suppresses IL-17 expression. IL-10 may be useful in the treatment of autoimmune diseases.
Heo
Yu-Jung
YJ
The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea, 505 Banpo-dong, Seocho-gu, Seoul 137-040, South Korea.
Joo
Young-Bin
YB
Oh
Hye-Jwa
HJ
Park
Mi-Kyung
MK
Heo
Yang-Mi
YM
Cho
Mi-La
ML
Kwok
Seung-Ki
SK
Ju
Ji-Hyeon
JH
Park
Kyung-Su
KS
Cho
Seok Goo
SG
Park
Sung-Hwan
SH
Kim
Ho-Youn
HY
Min
Jun-Ki
JK
D001172:Arthritis, Rheumatoid / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology; D015704:CD4 Antigens / Q000096:biosynthesis; D002478:Cells, Cultured; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000494:pharmacology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013582:Synovial Fluid / Q000166:cytology / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; C539900:RORC protein, human; D011994:Recombinant Proteins; D016753:Interleukin-10