Adjuvant treatment suppresses IL-17 production by T cell-independent myeloid sources in nonobese diabetic mice.
Recent studies have shown that Th17 cells, as a distinct lineage from Th1 and Th2 subsets, play an obligatory role in the pathogenesis of autoimmune diseases. It is well known that immunotherapy with Complete Freund's adjuvant (CFA) is effective in preventing from the onset of autoimmune diabetes in nonobese diabetic (NOD) mice. In the present study, we investigated whether CFA treatment restrained Th17 development and down-regulated Th17-related cytokine production in NOD mice. Th17-related cytokines (i.e. IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-6, TGF-beta) production in splenocytes was decreased dramatically on day 18 following CFA immunization. This effect was also observed at 10 and 20 week after adjuvant treatment. Injection of IL-17 into CFA-treated diabetes-free mice led to occurrence of overt diabetes, indicating that therapeutic effects of adjuvant treatment may be partially due to suppressing Th17 commitment. Interestingly, the main producer of IL-17 resided in a population of myeloid cells, which negatively expressed makers of neutrophil or macrophages. IL-23 stimulation did not alter the distribution of IL-17 in myeloid cells. Furthermore, this pattern of IL-17 expression was also present in Balb/c and C57BL/6 strains. These findings may have important implications for understanding of mechanisms underlying adjuvant treatment on autoimmune diseases.
Gao
Xiaogang
X
Department of Organ Transplantation, Shanghai ChangZheng Hospital, Second Military Medical University, 415 Feng Yang Road, Shanghai 200003, PR China.
Ding
Guoshan
G
Wang
Zhengxin
Z
Fu
Hong
H
Ni
Zhijia
Z
Ma
Jun
J
Song
Shaohua
S
Liu
Fang
F
Fu
Zhiren
Z
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D015551:Autoimmunity; D016207:Cytokines / Q000096:biosynthesis; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D015536:Down-Regulation; D005620:Freund's Adjuvant / Q000494:pharmacology; D007114:Immunization; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D053759:Interleukin-23 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D022423:Myeloid Cells / Q000276:immunology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013045:Species Specificity; D016176:T-Lymphocyte Subsets / Q000276:immunology
D000276:Adjuvants, Immunologic; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23; D011994:Recombinant Proteins; D005620:Freund's Adjuvant