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 CD69+CD103+ tissue-resident memory T cells (TRM) in the kidney. CD8+ TRM cells were expanded in the kidneys of patients with LN or MRL/lpr mice. The expansion of renal CD8+ TRM 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+ TRM cells underwent proliferation and self-renewal to maintain a stable TRM 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 TRM 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 TRM cells in the kidney, contributing to improved kidney function in MRL/lpr mice. These results provided evidences that renal CD8+ TRM cells play a role in the pathogenesis of LN. They could serve as a therapeutic target for LN.

中文翻译：

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JAK/STAT 信号控制 CD8+CD103+ 组织驻留记忆 T 细胞在狼疮性肾炎中的命运。

狼疮性肾炎 (LN) 中自身免疫介导的炎症和肾损伤部分取决于淋巴细胞在肾小球和肾间质中的浸润。在这里，我们在人类和小鼠的健康肾脏中鉴定了具有 CD103+ 表型的 CD8+ T 细胞群。这些细胞通常是肾脏中的 CD69+CD103+ 组织驻留记忆 T 细胞 (TRM)。CD8+ TRM 细胞在 LN 或 MRL/lpr 小鼠患者的肾脏中扩增。肾脏 CD8+ TRM 细胞的扩增与肾脏疾病活动显着相关。这些细胞在 MRL/lpr 小鼠肾脏中活跃地产生细胞因子、穿孔素和颗粒酶 B。重要的是，肾脏 CD8+ TRM 细胞经历增殖和自我更新以维持 MRL/lpr 小鼠肾脏中稳定的 TRM 池，从而导致肾脏炎症和损伤。MRL/lpr 小鼠中的 JAK/STAT 信号是肾脏 TRM 自我更新以及效应器功能维持所必需的。托法替尼靶向 JAK/STAT 信号传导有效抑制效应器功能并损害肾脏中肾 TRM 细胞的存活，有助于改善 MRL/lpr 小鼠的肾功能。这些结果提供了证据表明肾脏 CD8+ TRM 细胞在 LN 的发病机制中起作用。它们可以作为 LN 的治疗靶点。这些结果提供了证据表明肾脏 CD8+ TRM 细胞在 LN 的发病机制中起作用。它们可以作为 LN 的治疗靶点。这些结果提供了证据表明肾脏 CD8+ TRM 细胞在 LN 的发病机制中起作用。它们可以作为 LN 的治疗靶点。