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Conference proceeding
Macrophage/T cell Crosstalk for the Resolution of Inflammation
01 Jan 2022
Abstract
Macrophages play an active role in multiple phases of wound healing, transitioning from a predominantly pro-inflammatory (M1) population to less inflammatory, pro-regenerative phenotypes (M2). As high-level regulators of healing, macrophages pose a strong influence on other cell types through the secretion of cytokines and the expression of immunomodulatory ligands. Therefore, macrophages are an attractive target for cell therapies aiming to remedy dysfunctional wound healing characterized by chronic inflammation, such as that seen in aging patients. Previous work has shown that M2 macrophages that have previously been M1-activated, compared to those that have not, are phenotypically unique and exhibit enhanced M2 function. These “M1M2” macrophages are characterized by expression of the M2 marker CCL17, a chemokine known to attract skin-homing T cells, particularly IL-4-secreting Th2 cells and anti-inflammatory regulatory T cells (Tregs). This finding, along with the upregulation of immunosuppressive ligands PD-L1 and PD-L2 on M1 and M1M2 macrophages, respectively, begs the question of how macrophages may influence T cell differentiation (and vice versa) in the context of wound healing. In this study, we cultured human primary CD4+ T cells directly with autologous M0 or M1 macrophages, or with conditioned media generated by those phenotypes. After three days of co-culture, both macrophages and T cells were characterized via flow cytometry. Compared to T cells cultured alone, T cells co-cultured with macrophages exhibited increased differentiation into the Th2 and Treg phenotypes, and decreased differentiation into the inflammatory Th1 phenotype. These findings suggest that macrophages may direct the resolution of inflammation via crosstalk with T cells. Interestingly, similar results were seen in T cells cultured in macrophage-conditioned media, suggesting this crosstalk is not dependent on cell-cell interactions. Finally, macrophages co-cultured with T cells upregulated the expression of PD-L1, indicating that T cells may also promote immunosuppressive activity in macrophages.
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Details
- Title
- Macrophage/T cell Crosstalk for the Resolution of Inflammation
- Creators
- Erin O'BrienKara Spiller
- Publisher
- figshare
- Resource Type
- Conference proceeding
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991021811622004721