RNA-sequence analyses of PD-1hi CXCR5- Tph cells obtained from PBMC of healthy volunteers or patients with systemic lupus erythematosus.

PD-1hi CXCR5- T peripheral helper (Tph) cells produce IL-21 and contribute extra-follicular B cell activation in autoimmune diseases. However, it remains unclear what cytokines are required for Tph differentiation. We found that type I IFNs (IFN-alpha and IFN-beta) promote generation of IL-21-producing PD-1+ CXCR5- CD4+ T cells from human naïve CD4+ T cells cultured under IL-12 plus TGF-beta condition. To compare the gene expression pattern of T cells cultured in this condition with blood Tph cells, we performed RNA-seq analysis of Tph cells obtained from PBMC of healthy volunteers or patients with systemic lupus erythematosus.

程序性死亡受体1（PD-1）高表达、C-X-C趋化因子受体5（CXCR5）阴性的外周辅助性T（T peripheral helper，Tph）细胞可分泌白细胞介素21（IL-21），并在自身免疫疾病中促进滤泡外B细胞活化。然而，目前尚不清楚Tph细胞分化所需的细胞因子种类。本研究发现，I型干扰素（type I IFNs，包括IFN-α与IFN-β）可在白细胞介素12（IL-12）联合转化生长因子β（TGF-β）的培养条件下，从人初始CD4+T细胞（naïve CD4+ T cells）中诱导生成分泌IL-21的PD-1+CXCR5-CD4+T细胞。为对比该培养体系下的T细胞与血液Tph细胞的基因表达谱，我们对从健康志愿者或系统性红斑狼疮（systemic lupus erythematosus）患者外周血单个核细胞（peripheral blood mononuclear cells，PBMC）中分离得到的Tph细胞开展了RNA测序（RNA-seq）分析。