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PAQR11 modulates monocyte‐to‐macrophage differentiation and pathogenesis of rheumatoid arthritis
Immunology ( IF 4.9 ) Pub Date : 2021-01-09 , DOI: 10.1111/imm.13303 Yijun Lin 1 , Meiqin Huang 1 , Shuo Wang 1 , Xue You 1 , Lingling Zhang 1 , Yan Chen 1
Immunology ( IF 4.9 ) Pub Date : 2021-01-09 , DOI: 10.1111/imm.13303 Yijun Lin 1 , Meiqin Huang 1 , Shuo Wang 1 , Xue You 1 , Lingling Zhang 1 , Yan Chen 1
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During inflammation or tissue injury, pro‐inflammatory mediators attract migratory monocytes to inflammatory sites and monocyte‐to‐macrophage differentiation occurs to activate macrophages. We report here that PAQR11, a member of the progesterone and AdipoQ receptor family, regulates monocyte‐to‐macrophage differentiation in vitro and in vivo. Paqr11 gene was highly induced during monocyte‐to‐macrophage differentiation. Knockdown or deletion of Paqr11 inhibited monocyte differentiation but had little effect on macrophage polarization. Mechanistically, PAQR11 promoted cell survival as apoptosis was increased by Paqr11 knockdown or deletion. Activation of the MAPK signalling pathway was involved in the regulatory role of PAQR11 on monocyte differentiation and cell survival. C/EBPβ regulated the expression of Paqr11 at the transcriptional level. In mice, deletion of Paqr11 gene alleviated progression of collagen‐induced rheumatoid arthritis. Thus, these results provide strong evidence that PAQR11 has a function in monocyte‐to‐macrophage differentiation and such function is related to autoimmune disease in vivo.
中文翻译：
PAQR11 调节单核细胞向巨噬细胞的分化和类风湿性关节炎的发病机制
在炎症或组织损伤期间，促炎介质吸引迁移性单核细胞至炎症部位，并发生单核细胞向巨噬细胞分化以激活巨噬细胞。我们在此报告，PAQR11 是孕酮和 AdipoQ 受体家族的成员，在体外和体内调节单核细胞向巨噬细胞的分化。Paqr11基因在单核细胞向巨噬细胞分化过程中被高度诱导。Paqr11的敲低或缺失会抑制单核细胞分化，但对巨噬细胞极化影响不大。从机制上讲，PAQR11 促进细胞存活，因为Paqr11敲除或缺失会增加细胞凋亡。MAPK 信号通路的激活参与 PAQR11 对单核细胞分化和细胞存活的调节作用。C/EBPβ在转录水平调节Paqr11的表达。在小鼠中，Paqr11基因的缺失减轻了胶原蛋白诱导的类风湿性关节炎的进展。因此，这些结果提供了强有力的证据，表明PAQR11具有单核细胞向巨噬细胞分化的功能，并且这种功能与体内自身免疫性疾病有关。
更新日期：2021-01-09
中文翻译：
PAQR11 调节单核细胞向巨噬细胞的分化和类风湿性关节炎的发病机制
在炎症或组织损伤期间，促炎介质吸引迁移性单核细胞至炎症部位，并发生单核细胞向巨噬细胞分化以激活巨噬细胞。我们在此报告，PAQR11 是孕酮和 AdipoQ 受体家族的成员，在体外和体内调节单核细胞向巨噬细胞的分化。Paqr11基因在单核细胞向巨噬细胞分化过程中被高度诱导。Paqr11的敲低或缺失会抑制单核细胞分化，但对巨噬细胞极化影响不大。从机制上讲，PAQR11 促进细胞存活，因为Paqr11敲除或缺失会增加细胞凋亡。MAPK 信号通路的激活参与 PAQR11 对单核细胞分化和细胞存活的调节作用。C/EBPβ在转录水平调节Paqr11的表达。在小鼠中，Paqr11基因的缺失减轻了胶原蛋白诱导的类风湿性关节炎的进展。因此，这些结果提供了强有力的证据，表明PAQR11具有单核细胞向巨噬细胞分化的功能，并且这种功能与体内自身免疫性疾病有关。
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