Stratification of alopecia areata reveals involvement of CD4 T cell populations and altered faecal microbiota

Bain, K. A., Nichols, B., Kerbiriou, C., Moffat, F., Ijaz, U. Z. , Gerasimidis, K. , McInnes, I. B. , Åstrand, A., Holmes, S. and Milling, S. W. F. (2022) Stratification of alopecia areata reveals involvement of CD4 T cell populations and altered faecal microbiota. Clinical and Experimental Immunology, 210(2), pp. 175-186. (doi: 10.1093/cei/uxac088) (PMID:36200950) (PMCID:PMC9750826)

Abstract

Alopecia areata (AA) is an immune-mediated disease that causes non-scarring hair loss. Autoreactive CD8 T cells are key pathogenic effectors in the skin, and AA has been associated both with atopy and with perturbations in intestinal homeostasis. This study aimed to investigate mechanisms driving AA by characterizing the circulating immunophenotype and faecal microbiome, and by stratifying AA to understand how identified signatures associated with heterogeneous clinical features of the condition. Flow cytometric analyses identified alterations in circulating B cells and CD4 T cells, while 16S sequencing identified changes in alpha and beta diversity in the faecal microbiome in AA. The proportions of transitional and naïve B cells were found to be elevated in AA, particularly in AA samples from individuals with >50% hair loss and those with comorbid atopy, which is commonly associated with extensive hair loss. Although significant changes in circulating CD8 T cells were not observed, we found significant changes in CD4+ populations. In individuals with <50% hair loss higher frequencies of CCR6+CD4 (“Th17”) and CCR6+CXCR3+CD4 (“Th1/17”) T cells were found. While microbial species richness was not altered, AA was associated with reduced evenness and Shannon diversity of the intestinal microbiota, again particularly in those with <50% hair loss. We have identified novel immunological and microbial signatures in individuals with alopecia areata. Surprisingly, these are associated with lower levels of hair loss, and may therefore provide a rationale for improved targeting of molecular therapeutics.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: McInnes, Professor Iain and Kerbiriou, Caroline and Nichols, Mr Ben and Milling, Professor Simon and Bain, Miss Kym and Gerasimidis, Professor Konstantinos and Ijaz, Dr Umer
• Authors: Bain, K. A., Nichols, B., Kerbiriou, C., Moffat, F., Ijaz, U. Z., Gerasimidis, K., McInnes, I. B., Åstrand, A., Holmes, S., and Milling, S. W. F.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing; College of Science and Engineering > School of Engineering > Infrastructure and Environment
• Research Centre: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Immunobiology
• Journal Name: Clinical and Experimental Immunology
• Publisher: Oxford University Press
• ISSN: 0009-9104
• ISSN (Online): 1365-2249
• Published Online: 06 October 2022
• Copyright Holders: Copyright © 2022 The Authors
• First Published: First published in Clinical and Experimental Immunology 2022
• Publisher Policy: Reproduced under a Creative Commons License

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
170256		Understanding microbial community through in situ environmental 'omic data synthesis	Umer Zeeshan Ijaz	Natural Environment Research Council (NERC)	NE/L011956/1	ENG - Infrastructure & Environment