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. 2021 Mar 29;12:607204. doi: 10.3389/fimmu.2021.607204

Figure 3.

Figure 3

(A) Fibrosis induction: focus on MØs. DCs secrete high levels of CCR7 favoring lymphocyte recruitment. Pro-inflammatory M1 MØs secrete CCL2, CCL3 and CXCL8 that are chemoattractant for lymphocytes and monocytes. At the same time, M1 MØs produce inflammatory cytokines such as IL-6, IL-1ß and TNF-α that enhance the expression of adhesion molecules (V-CAM1/I-CAM1) by MCs promoting leukocyte adhesion. M2 MØs produce anti-inflammatory cytokines (IL-10) and lymphocyte chemoattracting chemokines (CCL17). Predominance of M2 MØ response leads to an increased TGF-ß1 secretion that induces MMT of MCs with up-regulation of ECM protein production. Moreover, MCs secreting CX3CL1 recruit MØs expressing CX3CR1. Receptor/ligand interaction determines a positive loop that promote, in turn, CX3CL1 and TGF-ß1 expression. (B) Fibrosis induction: focus on Th17/Treg balance. The production of IL-6 by MØs and MCs during the inflammatory process promotes IL-17 production by the peritoneal stroma which, in combination with IL-23, promotes the differentiation of Th17 lymphocytes. IL-17 promotes IL-1ß, TGF-ß1, VEGF and IL-6 production causing MMT induction and neoangiogenesis. Th17 abundance affects the activity of regulatory T lymphocytes. Treg lineage has an anti-inflammatory activity (due to IL-10 production) and protects the peritoneal membrane by mediating tolerance mechanisms. High levels of IL-6 and TGF-ß1 determine the predominance of Th17 over Treg with consequent peritoneal damage and fibrosis.