Webster, H. C., Gamino, V., Andrusaite, A. T., Ridgewell, O., McCowan, J., Shergold, A. L., Heieis, G. A., Milling, S. W.F. , Maizels, R. M. and Perona-Wright, G. (2022) Tissue-based IL-10 signalling in helminth infection limits IFNγ expression and promotes the intestinal Th2 response. Mucosal Immunology, 15(6), pp. 1257-1269. (doi: 10.1038/s41385-022-00513-y) (PMID:35428872) (PMCID:PMC9705258)
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Abstract
Type 2 immunity is activated in response to both allergens and helminth infection. It can be detrimental or beneficial, and there is a pressing need to better understand its regulation. The immunosuppressive cytokine IL-10 is known as a T helper 2 (Th2) effector molecule, but it is currently unclear whether IL-10 dampens or promotes Th2 differentiation during infection. Here we show that helminth infection in mice elicits IL-10 expression in both the intestinal lamina propria and the draining mesenteric lymph node, with higher expression in the infected tissue. In vitro, exogenous IL-10 enhanced Th2 differentiation in isolated CD4+ T cells, increasing expression of GATA3 and production of IL-5 and IL-13. The ability of IL-10 to amplify the Th2 response coincided with its suppression of IFNγ expression and in vivo we found that, in intestinal helminth infection, IL-10 receptor expression was higher on Th1 cells in the small intestine than on Th2 cells in the same tissue, or on any Th cell in the draining lymph node. In vivo blockade of IL-10 signalling during helminth infection resulted in an expansion of IFNγ+ and Tbet+ Th1 cells in the small intestine and a coincident decrease in IL-13, IL-5 and GATA3 expression by intestinal T cells. These changes in Th2 cytokines correlated with reduced expression of type 2 effector molecules, such as RELMα, and increased parasite egg production. Together our data indicate that IL-10 signalling promotes Th2 differentiation during helminth infection at least in part by regulating competing Th1 cells in the infected tissue.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Andrusaite, Ms Anna and Heieis, Graham Anthony and Shergold, Miss Amy and McCowan, Mr Jack and Ridgewell, Olivia and Milling, Professor Simon and Maizels, Professor Rick and Webster, Miss Holly and Perona-Wright, Dr Georgia |
| Authors: | Webster, H. C., Gamino, V., Andrusaite, A. T., Ridgewell, O., McCowan, J., Shergold, A. L., Heieis, G. A., Milling, S. W.F., Maizels, R. M., and Perona-Wright, G. |
| 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: | 15 April 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Mucosal Immunology 15(6): 1257-1269 |
| Publisher Policy: | Reproduced under a Creative Commons license |
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