IL-33–Stimulated Murine Mast Cells Polarize [..] Macrophages, ..Suppress T Cells That Mediate [..] Autoimmune Encephalomyelitis, 2020, Mills et al

Andy · Aug 30, 2020

Full title: IL-33–Stimulated Murine Mast Cells Polarize Alternatively Activated Macrophages, Which Suppress T Cells That Mediate Experimental Autoimmune Encephalomyelitis

IL-33 is known to promote type 2 immune responses through ST2, a component of the IL-33R complex, expressed primarily on mast cells, Th2 cells, group 2 innate lymphoid cells and regulatory T cells, and to a lesser extent, on NK cells and Th1 cells. Consistent with previous studies, we found that IL-33 polarized alternatively activated macrophages (AAMΦ) in vivo.

However, in vitro stimulation of murine bone marrow–derived or peritoneal macrophages with IL-33 failed to promote arginase activity or expression of YM-1 or Retnla, markers of AAMΦ. Furthermore, macrophages have low/no basal expression of ST2. This suggested that alternative activation of macrophages may involve an IL-33–responsive third-party cell.

Because mast cells have the highest expression of ST2 relative to other leukocytes, we focused on this cell type. Coculture experiments showed that IL-33–stimulated mast cells polarized AAMΦ through production of soluble factors. IL-33–stimulated mast cells produced a range of cytokines, including IL-6 and IL-13. Mast cell–derived IL-13 was required for induction of AAMΦ, whereas mast cell–derived IL-6 enhanced macrophage responsiveness to IL-13 via upregulation of the IL-4Rα receptor. Furthermore, we found that AAMΦ polarized by IL-33–stimulated mast cells could suppress proliferation and IL-17 and IFN-γ production by T cells.

Finally, we show that AAMΦ polarized by IL-33–stimulated mast cells attenuated the encephalitogenic function of T cells in the experimental autoimmune encephalomyelitis model. Our findings reveal that IL-33 can promote immunosuppressive responses by polarizing AAMΦ via mast cell–derived IL-6 and IL-13.
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Paywall, https://www.jimmunol.org/content/early/2020/08/27/jimmunol.1901321
Sci hub, https://sci-hub.tw/10.4049/jimmunol.1901321

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IL-33–Stimulated Murine Mast Cells Polarize [..] Macrophages, ..Suppress T Cells That Mediate [..] Autoimmune Encephalomyelitis, 2020, Mills et al

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IL-33–Stimulated Murine Mast Cells Polarize [..] Macrophages, ..Suppress T Cells That Mediate [..] Autoimmune Encephalomyelitis, 2020, Mills et al

Andy Committee Member

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