Quintana, J. F. et al. (2023) γδ T cells control murine skin inflammation and subcutaneous adipose wasting during chronic Trypanosoma brucei infection. Nature Communications, 14, 5279. (doi: 10.1038/s41467-023-40962-y) (PMID:37644007) (PMCID:PMC10465518)
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Abstract
African trypanosomes colonise the skin to ensure parasite transmission. However, how the skin responds to trypanosome infection remains unresolved. Here, we investigate the local immune response of the skin in a murine model of infection using spatial and single cell transcriptomics. We detect expansion of dermal IL-17A-producing Vγ6+ cells during infection, which occurs in the subcutaneous adipose tissue. In silico cell-cell communication analysis suggests that subcutaneous interstitial preadipocytes trigger T cell activation via Cd40 and Tnfsf18 signalling, amongst others. In vivo, we observe that female mice deficient for IL-17A-producing Vγ6+ cells show extensive inflammation and limit subcutaneous adipose tissue wasting, independently of parasite burden. Based on these observations, we propose that subcutaneous adipocytes and Vγ6+ cells act in concert to limit skin inflammation and adipose tissue wasting. These studies provide new insights into the role of γδ T cell and subcutaneous adipocytes as homeostatic regulators of skin immunity during chronic infection.
| Item Type: | Articles |
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| Additional Information: | This work was funded by a Sir Henry Wellcome postdoctoral fellowship (221640/Z/20/Z to JFQ), a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ), a University of Glasgow Lord Kelvin Adam Smith Leadership Fellowship (to JFQ), and a Wellcome Trust Senior Research fellow (209511/Z/17/Z to AML). RH is a Wellcome Trust PhD student (Wellcome Trust 218518/Z/19/Z). MCS, PC, JO, AC, and NRK are supported by a Wellcome Trust Senior Research fellowship (209511/Z/17/Z) awarded to AML. JO is also supported by a Wellcome Trust FutureScope grant (104111/Z/14/Z Wellcome Centre for Integrative Parasitology to JFQ). SBC is supported by a grant from the Annie McNab Bequest (CRUK Beatson Institute), Breast Cancer Now (2018JulPR1101, 2019DecPhD1349, 2019DecPR1424), Cancer Research Institute (CLIP award), Cancer Research UK (RCCCEA-Nov21\100003, EDDPGM-Nov21\100001, DRCNPG-Jun22\100007), and Pancreatic Cancer Research and Worldwide Cancer Research (22-0135). NAM is supported by a BBSRC Institute Strategic Programme (BBS/E/D/20002173 and BB/X010937/1). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Sinton, Dr Matthew and Coffelt, Professor Seth and Swar, Mr Nono-Raymond and MacLeod, Professor Annette and Lestari, Miss Agatha and Ogunsola, Mr John and Quintana, Dr Juan and Cooper, Dr Anneli and Cheaib, Dr Bachar and Heslop, Rhiannon and Chandrasegaran, Miss Praveena |
| Authors: | Quintana, J. F., Sinton, M. C., Chandrasegaran, P., Lestari, A. N., Heslop, R., Cheaib, B., Ogunsola, J., Ngoyi, D. M., Swar, N.-R. K., Cooper, A., Mabbott, N. A., Coffelt, S. B., and MacLeod, A. |
| College/School: | College of Medical Veterinary and Life Sciences College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
| Journal Name: | Nature Communications |
| Publisher: | Nature Research |
| ISSN: | 2041-1723 |
| ISSN (Online): | 2041-1723 |
| Copyright Holders: | Copyright © 2023 The Authors |
| First Published: | First published in Nature Communications 14:5279 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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