Kornstädt, L.L.KornstädtPierre, S.S.PierreWeigert, A.A.WeigertEbersberger, S.S.EbersbergerSchäufele, T.J.T.J.SchäufeleKolbinger, A.A.KolbingerSchmid, T.T.SchmidCohnen, J.J.CohnenThomas, D.D.ThomasFerreirós, N.N.FerreirósBrüne, B.B.BrüneEbersberger, I.I.EbersbergerScholich, K.K.Scholich2022-03-062022-03-062021https://publica.fraunhofer.de/handle/publica/26889410.3389/fimmu.2020.607048Next to their role in IgE-mediated allergic diseases and in promoting inflammation, mast cells also have antiinflammatory functions. They release pro- as well as antiinflammatory mediators, depending on the biological setting. Here we aimed to better understand the role of mast cells during the resolution phase of a local inflammation induced with the Toll-like receptor (TLR)-2 agonist zymosan. Multiple sequential immunohistology combined with a statistical neighborhood analysis showed that mast cells are located in a predominantly antiinflammatory microenvironment during resolution of inflammation and that mast cell-deficiency causes decreased efferocytosis in the resolution phase. Accordingly, FACS analysis showed decreased phagocytosis of zymosan and neutrophils by macrophages in mast cell-deficient mice. mRNA sequencing using zymosan-induced bone marrow-derived mast cells (BMMC) revealed a strong type I interferon (IFN) response, which is known to enhance phagocytosis by macrophages. Both, zymosan and lipopolysaccharides (LPS) induced IFN-v synthesis in BMMCs in similar amounts as in bone marrow derived macrophages. IFN-v was expressed by mast cells in paws from naïve mice and during zymosan-induced inflammation. As described for macrophages the release of type I IFNs from mast cells depended on TLR internalization and endosome acidification. In conclusion, mast cells are able to produce several mediators including IFN-v, which are alone or in combination with each other able to regulate the phagocytotic activity of macrophages during resolution of inflammation.en540616571572journal article