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Differential Modulation of Human M1 and M2 Macrophage Activity by ICOS-Mediated ICOSL Triggering.

ABSTRACT: Activated T cells express the inducible T-cell co-stimulator (ICOS) that, upon binding to its ubiquitously expressed ligand (ICOSL), regulates the immune response and tissue repair. We sought to determine the effect of ICOS:ICOSL interaction on human M1 and M2 macrophages. M1 and M2 macrophages were polarized from monocyte-derived macrophages, and the effect of a soluble recombinant form of ICOS (ICOS-CH3) was assessed on cytokine production and cell migration. We show that ICOS-CH3 treatment increased the secretion of CCL3 and CCL4 in resting M1 and M2 cells. In LPS-treated M1 cells, ICOS-CH3 inhibited the secretion of TNF-α, IL-6, IL-10 and CCL4, while it increased that of IL-23. In contrast, M2 cells treated with LPS + IL4 displayed enhanced secretion of IL-6, IL-10, CCL3 and CCL4. In CCL7- or osteopontin-treated M1 cells, ICOS-CH3 boosted the migration rate of M1 cells while it decreased that of M2 cells. Finally, β-Pix expression was upregulated in M1 cells and downregulated in M2 cells by treatment with ICOS-CH3. These findings suggest that ICOSL activation modulates the activity of human M1 and M2 cells, thereby eliciting an overall anti-inflammatory effect consistent with its role in promoting tissue repair.

SUBMITTER: Gigliotti CL

PROVIDER: S-EPMC9917690 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Differential Modulation of Human M1 and M2 Macrophage Activity by ICOS-Mediated ICOSL Triggering.

Gigliotti Casimiro Luca CL Dianzani Chiara C Stoppa Ian I Monge Chiara C Sutti Salvatore S Sblattero Daniele D Puricelli Chiara C Rolla Roberta R Dianzani Umberto U Boggio Elena E

International journal of molecular sciences 20230202 3

Activated T cells express the inducible T-cell co-stimulator (ICOS) that, upon binding to its ubiquitously expressed ligand (ICOSL), regulates the immune response and tissue repair. We sought to determine the effect of ICOS:ICOSL interaction on human M1 and M2 macrophages. M1 and M2 macrophages were polarized from monocyte-derived macrophages, and the effect of a soluble recombinant form of ICOS (ICOS-CH3) was assessed on cytokine production and cell migration. We show that ICOS-CH3 treatment in ...[more]

PMID: 36769276

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Project description:IntroductionThe underlying cause of psoriasis, a chronic inflammatory skin condition driven by an immune response, remains a topic of active investigation and is not yet fully elucidated. Recent studies have revealed that ergothioneine, a small molecule sulfur-containing histidine derivative that can be ingested from the daily diet and accumulated in the body, exhibits antioxidant capacity that is comparable to that of glutathione. Nevertheless, there is a paucity of empirical data concerning the precise impact of ergothioneine in the context of anti-inflammatory processes, particularly in the context of psoriasis. In the light of the aforementioned considerations, the present study was undertaken with the objective of conducting a comprehensive evaluation of the anti-inflammatory potential of ergothioneine (EGT) and to investigate its potential impact on the pathogenesis of psoriasis.MethodsThe efficacy of EGT in reducing the extent of dorsal skin lesions in psoriasis model mice was confirmed through in vivo experimental observation. Furthermore, the inhibitory effect of EGT on inflammatory responses at the cellular level was investigated, specifically in LPS-induced mouse macrophage (RAW264.7) and human keratinocyte-forming cell (HaCaT) models.ResultsThe results demonstrated that the introduction of different concentrations of EGT into the LPS-induced inflammatory cell model resulted in notable anti-inflammatory effects, as evidenced by a reduction in inflammatory responses and a dose dependent decline in the concentrations of key inflammatory cytokines, including interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) and tumour necrosis factor-α (TNF-α). Furthermore, EGT was observed to reverse the LPS induced increase in the ratio of M1 to M2 macrophages. EGT was also observed to markedly suppress the LPS-induced phosphorylation of JAK/STAT3 and NF-κB, offering a novel insight into the anti-inflammatory mechanism of EGT.DiscussionIn conclusion, the findings of the present study consistently demonstrated that ergothioneine had a significant ameliorative effect on the imiquimod-induced psoriasis model by modulating the NF-κB/JAK-STAT3 signalling pathway. This provides a strong experimental rationale for its potential application in psoriasis treatment.

Dataset Information

Differential Modulation of Human M1 and M2 Macrophage Activity by ICOS-Mediated ICOSL Triggering.

Publications

Differential Modulation of Human M1 and M2 Macrophage Activity by ICOS-Mediated ICOSL Triggering.

Similar Datasets

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