FcγR‐dependent apoptosis regulates tissue persistence of mucosal and connective tissue mast cells

• Published in: European journal of immunology 2023-08, Vol.53 (8), p.e2250221-n/a
• Main Authors: Wu, Tongqian, Yan, Shirong, Yeh, Yu‐Wen, Fang, Yu, Xiang, Zou
• Format: Article
• Language: English
• Subjects: Animals; antigen; Apoptosis; Caspase; Cell number; Connective tissue; Connective Tissue - metabolism; Connective Tissue Cells - metabolism; connective tissue mast cell; Connective tissues; disease; expression; Fc gamma receptor; Fcγ receptor; igg receptors; Immunoglobulin G; Immunologi inom det medicinska området; Immunology; Immunology in the medical area; Life span; ligand; mast cell; Mast Cells; Mice; mouse; Mucosa; mucosal mast cell; rat; Receptors, IgG - genetics; Receptors, IgG - metabolism; rii
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.202250221

Rodent mast cells can be divided into two major subtypes: the mucosal mast cell (MMC) and the connective tissue mast cell (CTMC). A decade‐old observation revealed a longer lifespan for CTMC compared with MMC. The precise mechanisms underlying such differential tissue persistence of mast cell subsets have not been described. In this study, we have discovered that mast cells expressing only one receptor, either FcγRIIB or FcγRIIIA, underwent caspase‐independent apoptosis in response to IgG immune complex treatment. Lower frequencies of CTMC in mice that lacked either FcγRIIB or FcγRIIIA compared with WT mice were recorded, especially in aged mice. We proposed that this paradigm of FcγR‐mediated mast cell apoptosis could account for the more robust persistence of CTMC, which express both FcγRIIB and FcγRIIIA, than MMC, which express only FcγRIIB. Importantly, we reproduced these results using a mast cell engraftment model, which ruled out possible confounding effects of mast cell recruitment or FcγR expression by other cells on mast cell number regulation. In conclusion, our work has uncovered an FcγR‐dependent mast cell number regulation paradigm that might provide a mechanistic explanation for the long‐observed differential mast cell subset persistence in tissues. Connective tissue mast cells (CTMC), which express both FcγRIIB and FcγRIIIA, have a longer life span than mucosal mast cells (MMC), which express only FcγRIIB. Cell death induction upon IgG immune complex‐mediated aggregation of FcγRIIB may explain the long‐observed differential tissue persistence of these two rodent mast cell subsets.