Dysregulation of IL-34 ligation to SDC-1 mitigates collagen-induced arthritis.
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ABSTRACT:
SUBMITTER: Meyer A
PROVIDER: S-EPMC9424265 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Dysregulation of IL-34 ligation to SDC-1 mitigates collagen-induced arthritis.
Meyer Anja A Sienes Ryan R Zanotti Brian B van Raemdonck Katrien K Palasiewicz Karol K Mass Daniel P DP Volin Michael V MV Shahrara Shiva S
Cellular & molecular immunology 20220608 9
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Project description:Murine gammadelta T cell subsets, defined by their Vgamma chain usage, have been shown in various disease models to have distinct functional roles. In this study, we examined the responses of the two main peripheral gammadelta T cell subsets, Vgamma1(+) and Vgamma4(+) cells, during collagen-induced arthritis (CIA), a mouse model that shares many hallmarks with human rheumatoid arthritis. We found that whereas both subsets increased in number, only the Vgamma4(+) cells became activated. Surprisingly, these Vgamma4(+) cells appeared to be Ag selected, based on preferential Vgamma4/Vdelta4 pairing and very limited TCR junctions. Furthermore, in both the draining lymph node and the joints, the vast majority of the Vgamma4/Vdelta4(+) cells produced IL-17, a cytokine that appears to be key in the development of CIA. In fact, the number of IL-17-producing Vgamma4(+) gammadelta T cells in the draining lymph nodes was found to be equivalent to the number of CD4(+)alphabeta(+) Th-17 cells. When mice were depleted of Vgamma4(+) cells, clinical disease scores were significantly reduced and the incidence of disease was lowered. A decrease in total IgG and IgG2a anti-collagen Abs was also seen. These results suggest that Vgamma4/Vdelta4(+) gammadelta T cells exacerbate CIA through their production of IL-17.
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