A novel CD4+ T cell population expanded in Systemic Lupus Erythematosus (SLE) blood provides B cell help through IL10 and succinate

A better understanding of the molecular and cellular factors involved in human plasma cell differentiation will accelerate therapeutic target identification in autoantibody-mediated diseases such as Systemic Lupus Erythematosus (SLE). Here, we describe a novel CXCR3+ PD1hi CD4+ T cell 'helper' population expanded in blood and inflamed kidneys of SLE patients. Upon activation, these cells express IFNg and IL10 and display high levels of mitochondrial ROS (mtROS) as the result of reverse electron transfer (RET) fueled by succinate. Furthermore, T cell-derived succinate synergizes with IL10 to provide B cell help. Cells with similar phenotype and function are generated in vitro upon priming naive CD4+ T cells with oxidized mitochondrial DNA (Ox mtDNA)- activated plasmacytoid dendritic cells (pDCs) in a PD1-dependent manner. Our results provide a novel mechanism for the initiation and/or perpetuation of extrafollicular humoral responses in SLE. Overall design: 2 independent datasets; dataset1: total 9 samples (3 subjects, 3 groups, 3 replicates); dataset2: total 20 samples, 2 samples(PD1POS, Tfh) from each of 10 SLE patients

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Caielli S, Veiga DT, Balasubramanian P, Athale S, Domic B, Murat E, Banchereau R, Xu Z, Chandra M, Chung CH, Walters L, Baisch J, Wright T, Punaro M, Nassi L, Stewart K, Fuller J, Ucar D, Ueno H, Zhou J, Banchereau J, Pascual V