IL-25 attenuates rheumatoid arthritis through suppression of Th17 immune responses in an IL-13-dependent manner.
IL-25, a new member of the IL-17 cytokine family, is involved in type 2 immunity initiation and has been associated with the pathogenesis of rheumatoid arthritis (RA). However, its exact role remains unclear. Here, we aimed to analyse IL-25 expression in the serum and synovial fluid of RA patients and evaluated the correlations between serum IL-25 levels, clinical and laboratory values and inflammation cytokines. Additionally, we investigated whether IL-25 can suppress Th1/Th17 responses involved in RA pathogenesis. We further determined whether IL-25 can alleviate collagen-induced arthritis (CIA) development in mice and the underlying mechanisms using in vitro and in vivo experiments. Our results showed that IL-25 was upregulated in the serum and synovial fluid of RA patients. Increased serum IL-25 levels were associated with disease severity and inflammatory response in RA patients. Furthermore, IL-25 inhibited CD4+T-cell activation and differentiation into Th17 cells, without affecting Th1 cells in human RA and CIA models. Administration of IL-25 could attenuate CIA development by Th17 suppression in an IL-13-dependent manner. Our findings indicate that IL-25 plays a potent immunosuppressive role in the pathogenesis of RA and CIA by downregulating Th17 cell response, and thus, may be a potential therapeutic agent for RA.
Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.|Departement of Rheumatology and Immunology, Xi'an No. 5 Hospital, Xi'an, Shaanxi 710082, China.|Xi'an Institute of Rheumatology, Xi'an, Shaanxi 710082, China.
Dan
D
Liu
Departement of Rheumatology and Immunology, Xi'an No. 5 Hospital, Xi'an, Shaanxi 710082, China.
Tuanping
T
Cao
Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Na
N
Wang
Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Chengfei
C
Liu
Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Ning
N
Ma
College of Life Sciences, Shaanxi Normal University, Xi'an, Shaanxi 710062, China.
Ran
R
Tu
Core Research Laboratory, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China.
Xiaoyun
X
Min
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D002454:Cell Differentiation; D005260:Female; D006801:Humans; D007108:Immune Tolerance; D018793:Interleukin-13 / Q000276:immunology*; D020381:Interleukin-17 / Q000097:blood / Q000276:immunology*; D007378:Interleukins / Q000276:immunology / Q000627:therapeutic use; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013582:Synovial Fluid / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology
C578095:IL13 protein, human; C486701:IL25 protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D007378:Interleukins; C442281:Mydgf protein, mouse