JAK/STAT signaling controls the fate of CD8CD103 tissue-resident memory T cell in lupus nephritis.

Autoimmune mediated inflammation and renal damage in lupus nephritis (LN) depends partly on the infiltration of lymphocytes in glomeruli and renal interstitium. Here we identified a population of CD8 T cells with a CD103-phenotype in the healthy kidneys of human and mouse. These cells were typically CD69CD103 tissue-resident memory T cells (T) in the kidney. CD8 T cells were expanded in the kidneys of patients with LN or MRL/lpr mice. The expansion of renal CD8 T cells correlated significantly with kidney disease activity. These cells were active in producing cytokines, perforin and granzyme B in the kidney of MRL/lpr mice. Importantly, renal CD8 T cells underwent proliferation and self-renewal to maintain a stable T pool in the kidney of MRL/lpr mice, contributing to renal inflammation and damage. JAK/STAT signaling in the MRL/lpr mice was required for renal T self-renewal as well as maintenance of effector functions. Targeting JAK/STAT signaling by tofacitinib effectively suppressed effector functions and impaired the survival of renal T cells in the kidney, contributing to improved kidney function in MRL/lpr mice. These results provided evidences that renal CD8 T cells play a role in the pathogenesis of LN. They could serve as a therapeutic target for LN.