Varyani, F. et al. (2022) The IL-25-dependent tuft cell circuit driven by intestinal helminths requires macrophage migration inhibitory factor (MIF). Mucosal Immunology, 15(6), pp. 1243-1256. (doi: 10.1038/s41385-022-00496-w) (PMID:35288645) (PMCID:PMC9705247)
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Abstract
Macrophage migration inhibitory factor (MIF) is a key innate immune mediator with chemokine- and cytokine-like properties in the inflammatory pathway. While its actions on macrophages are well-studied, its effects on other cell types are less understood. Here we report that MIF is required for expansion of intestinal tuft cells during infection with the helminth Nippostrongylus brasiliensis. MIF-deficient mice show defective innate responses following infection, lacking intestinal epithelial tuft cell hyperplasia or upregulation of goblet cell RELMβ, and fail to expand eosinophil, type 2 innate lymphoid cell (ILC2) and macrophage (M2) populations. Similar effects were observed in MIF-sufficient wild-type mice given the MIF inhibitor 4-IPP. MIF had no direct effect on epithelial cells in organoid cultures, and MIF-deficient intestinal stem cells could generate tuft cells in vitro in the presence of type 2 cytokines. In vivo the lack of MIF could be fully compensated by administration of IL-25, restoring tuft cell differentiation and goblet cell expression of RELM-β, demonstrating its requirement upstream of the ILC2-tuft cell circuit. Both ILC2s and macrophages expressed the MIF receptor CXCR4, indicating that MIF may act as an essential co-factor on both cell types to activate responses to IL-25 in helminth infection.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Drurey, Claire and Varyani, Dr Fumi and White, Dr Madeleine and Campillo Poveda, Dr Marta and Rasid, Dr Orhan and Maizels, Professor Rick and Smyth, Dr Danielle |
| Creator Roles: | Varyani, F.Investigation, Formal analysis, Writing – original draft, Writing – review and editing Drurey, C.Investigation Rasid, O.Investigation Smyth, D. J.Investigation Maizels, R. M.Formal analysis, Writing – original draft, Writing – review and editing |
| Authors: | Varyani, F., Löser, S., Filbey, K. J., Harcus, Y., Drurey, C., Poveda, M. C., Rasid, O., White, M. P.J., Smyth, D. J., Gerbe, F., Jay, P., and Maizels, R. M. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Research Centre: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology |
| Journal Name: | Mucosal Immunology |
| Publisher: | Springer Nature |
| ISSN: | 1933-0219 |
| ISSN (Online): | 1935-3456 |
| Published Online: | 14 March 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Mucosal Immunology 15(6): 1243-1256 |
| Publisher Policy: | Reproduced under a Creative Commons licence |
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