Mesenchymal stem/stromal cells primed by inflammatory cytokines alleviate psoriasis-like inflammation via the TSG-6-neutrophil axis

• DOI: 10.1038/s41419-022-05445-w
• Publication Date: 2022-11-25T21:32:02Z
• Authors: Yayun Ding; Pixia Gong; Junjie Jiang; Chao Feng; Yanan Li; Xiao Su; Xiaojing Bai; Chenchang Xu; Chunxiao Liu; Jianxin Yang; Jiankai Fang; Xiaocao Ji; Yongjing Chen; Peishan Li; Lingchuan Guo; Changshun Shao; Yufang Shi
• Keywords: Inflammation; 0301 basic medicine; QH573-671; Neutrophils; Tumor Necrosis Factor-alpha; Mesenchymal Stem Cells; Article; 3. Good health; Mice; 03 medical and health sciences; Animals; Humans; Cytokines; Immunologic Factors; Psoriasis; Cytology; Cell Adhesion Molecules

AbstractPsoriasis is currently an incurable skin disorder mainly driven by a chronic inflammatory response. We found that subcutaneous application of umbilical cord- derived mesenchymal stem/stromal cells (MSCs) primed by IFN-γ and TNF-α, referred to as MSCs-IT, exhibited remarkable therapeutic efficacy on imiquimod (IMQ)-induced psoriasis-like inflammation in mice. Neutrophil infiltration, a hallmark of psoriasis, was significantly reduced after treatment with MSCs-IT. We further demonstrated that the effects of MSCs-IT were mediated by tumor necrosis factor (TNF) stimulating gene-6 (TSG-6), which was greatly upregulated in MSCs upon IFN-γ and TNF-α stimulation. MSCs transduced with TSG-6 siRNA lost their therapeutic efficacy while recombinant TSG-6 applied alone could also reduce neutrophil infiltration and alleviate the psoriatic lesions. Furthermore, we demonstrated that TSG-6 could inhibit neutrophil recruitment by decreasing the expression of CXCL1, which may be related to the reduced level of STAT1 phosphorylation in the keratinocytes. Thus, blocking neutrophil recruitment by MSCs-IT or TSG-6 has potential for therapeutic application in human psoriasis.