Aberrant population expansion of follicular helper T cells (T_FH cells) occurs in patients with lupus. An unanswered question is whether an altered repertoire of T cell antigen receptors (TCRs) is associated with such expansion. Here we found that the transcription factor Blimp-1 (encoded by Prdm1) repressed expression of the gene encoding cathepsin S (Ctss), a cysteine protease that cleaves invariant chains and produces antigenic peptides for loading onto major histocompatibility complex (MHC) class II molecules. The increased CTSS expression in dendritic cells (DCs) from female mice with dendritic cell-specific conditional knockout of Prdm1 (CKO mice) altered the presentation of antigen to CD4⁺ T cells. Analysis of complementarity-determining region 3 (CDR3) regions containing the β-chain variable region (V_β) demonstrated a more diverse repertoire of T_FH cells from female CKO mice than of those from wild-type mice. In vivo treatment of CKO mice with a CTSS inhibitor abolished the lupus-related phenotype and reduced the diversity of the T_FH cell TCR repertoire. Thus, Blimp-1 deficiency in DCs led to loss of appropriate regulation of Ctss expression in female mice and thereby modulated antigen presentation and the T_FH cell repertoire to contribute to autoimmunity.

中文翻译：

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Prdm1-/-树突状细胞中组织蛋白酶S的增加会改变TFH细胞的组成，并导致狼疮。

狼疮患者发生滤泡辅助性T细胞（_TFH细胞）的异常扩增。一个尚未解决的问题是，T细胞抗原受体（TCR）组成的改变是否与这种扩增有关。在这里我们发现转录因子Blimp-1（由Prdm1编码）抑制了组织蛋白酶S（Ctss）的基因的表达，这是一种半胱氨酸蛋白酶，可切割恒定链并产生抗原性肽，以装载到主要的组织相容性复合体（MHC）II类分子上。具有Prdm1的树突细胞特异性条件性敲除的雌性小鼠的树突细胞（DC）中CTSS表达的增加（CKO小鼠）改变了抗原向CD4 ⁺的呈递T细胞。互补决定区3的分析含有β链可变区（V（CDR3）的区域_β）证明T的更多样化的库_FH细胞从雌性小鼠CKO比来自野生型小鼠的。用CTSS抑制剂对CKO小鼠进行体内治疗可消除狼疮相关的表型，并减少T _FH细胞TCR组成的多样性。因此，飞艇-1缺陷DCs中导致雌性小鼠CTSS表达的适当调节的损失，并由此调制抗原呈递和T _FH细胞库有助于自身免疫。