CD30L is involved in the regulation of the inflammatory response through inducing homing and differentiation of monocytes via CCL2/CCR2 axis and NF-κB pathway in mice with colitis.

Chenxue Mei, Fanxiang Meng, Xiao Wang, Siqi Yan, Qianqian Zheng, Xiaoqing Zhang, Wenda Fu, Junxiu Xue, Shengyi Wang, Yan He, Xun Sun, Xuefeng Jiang, Yuanyuan Wang

International immunopharmacology 2022 Sep

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The pathogenesis of inflammatory bowel diseases (IBD) is complex, and dysregulated immune responses play a pivotal role in its occurrence and development. Our previous studies indicated that CD30L may participate in monocyte-mediated inflammation in patients with UC through the activation of circulating monocytes. However, it remains unclear how CD30L participates in monocyte-mediated inflammation in IBD by activation of circulating monocytes. In this study, we observed an increase in the expression of CD30L and chemokine receptor type 2 (CCR2) on circulating monocytes and pro-inflammatory monocytes in the colon lamina propria in mice with dextran sulfate sodium salt (DSS)-induced colitis. Moreover, there was a positive correlation between the expression levels of CCR2 and CD30L (r = 0.8817, p = 0.0480) in monocytes. In Cd30l-/- mice with DSS-induced colitis, the percentage and absolute number of circulating monocytes and pro-inflammatory monocytes decreased with the downregulation of CCR2. Stimulation via CD30L by immobilized anti-CD30L mAb suppressed the expression of pNF-κB p65, pIκBα, p65 and CCR2 and up-regulated the expression of IκBα in the sorted pro-inflammatory monocytes in Cd30l-/- mice with DSS-induced colitis. The mRNA levels of Ccr2 in the sorted pro-inflammatory monocytes were significantly down-regulated with the presence of immobilized RM153 and inhibitors of NF-κB (BAY 11-7082) in WT mice with DSS-induced colitis. Our results suggested that CD30L could promote the inflammatory response by inducing the homing and differentiation of monocytes via the chemokine ligand 2 (CCL2)/CCR2 axis and NF-κB signaling pathway in mice with colitis. These findings provide a novel target for monocyte-based immunotherapy against IBD. Copyright © 2022. Published by Elsevier B.V.

Citation

Chenxue Mei, Fanxiang Meng, Xiao Wang, Siqi Yan, Qianqian Zheng, Xiaoqing Zhang, Wenda Fu, Junxiu Xue, Shengyi Wang, Yan He, Xun Sun, Xuefeng Jiang, Yuanyuan Wang. CD30L is involved in the regulation of the inflammatory response through inducing homing and differentiation of monocytes via CCL2/CCR2 axis and NF-κB pathway in mice with colitis. International immunopharmacology. 2022 Sep;110:108934