Early-life antibiotic treatment enhances the pathogenicity of CD4 + T cells during intestinal inflammation

Scheer, S. et al. (2017) Early-life antibiotic treatment enhances the pathogenicity of CD4 + T cells during intestinal inflammation. Journal of Leukocyte Biology, 101(4), pp. 893-900. (doi: 10.1189/jlb.3MA0716-334RR) (PMID:28034915)

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The incidence of inflammatory bowel diseases (IBDs) has steadily increased in recent decades—a phenomenon that cannot be explained by genetic mutations alone. Other factors, including the composition of the intestinal microbiome, are potentially important contributors to the increased occurrence of this group of diseases. Previous reports have shown a correlation between early-life antibiotic (Abx) treatment and an increased incidence of IBD. In this report, we investigated the effects of early-life Abx treatments on the pathogenicity of CD4+ T cells using an experimental T cell transfer model of IBD. Our results show that CD4+ T cells isolated from adult mice that had been treated with Abx during gestation and in early life induced a faster onset of IBD in Rag1-deficient mice compared with CD4+ T cells of untreated mice. Ex vivo functional analyses of IBD-inducing CD4+ T cells did not show significant differences in their immunologic potential ex vivo, despite their in vivo phenotype. However, genome-wide gene-expression analysis revealed that these cells displayed dysregulated expression of genes associated with cell-cycle regulation, metabolism, and cellular stress. Analysis of Abx-treated CD4+ T cell donors showed systemically elevated levels of the stress hormone corticosterone throughout life compared with untreated donors. The cohousing of Abx-treated mice with untreated mice decreased serum corticosterone, and a consequent transfer of the cells from cohoused mice into Rag1-deficient mice restored the onset and severity of disease to that of untreated animals. Thus, our results suggest that early-life Abx treatment results in a stress response with high levels of corticosterone that influences CD4+ T cell function.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Perona-Wright, Dr Georgia
Authors: Scheer, S., Medina, T. S., Murison, A., Taves, M. D., Antignano, F., Chenery, A., Soma, K. K., Perona-Wright, G., Lupien, M., Arrowsmith, C. H., De Carvalho, D. D., and Zaph, C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Journal of Leukocyte Biology
Publisher:Society for Leukocyte Biology
ISSN (Online):1938-3673
Published Online:29 December 2016

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