FLG Deficiency in Mice Alters the Early-Life CD4 + T-Cell Response to Skin Commensal Bacteria.

Autor:	Gonzalez JR; Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA., Celli A; Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Dermatology Service, San Francisco VA Medical Center, San Francisco, California, USA., Weckel A; Department of Dermatology, University of California San Francisco, San Francisco, California, USA., Dhariwala MO; Department of Dermatology, University of California San Francisco, San Francisco, California, USA., Merana GR; Department of Dermatology, University of California San Francisco, San Francisco, California, USA., Ojewumi OT; Department of Dermatology, University of California San Francisco, San Francisco, California, USA., Okoro J; Department of Dermatology, University of California San Francisco, San Francisco, California, USA., Dwyer LR; Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA., Tran VM; Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Biomedical Sciences Graduate Program, University of California San Francisco, San Francisco, California, USA., Meyer JM; Department of Dermatology, Vanderbilt University Medical Center, Nashville, Tennesse, USA., Mauro TM; Department of Dermatology, University of California San Francisco, San Francisco, California, USA; Dermatology Service, San Francisco VA Medical Center, San Francisco, California, USA., Scharschmidt TC; Department of Dermatology, University of California San Francisco, San Francisco, California, USA. Electronic address: Tiffany.scharschmidt@ucsf.edu.
Jazyk:	angličtina
Zdroj:	The Journal of investigative dermatology [J Invest Dermatol] 2023 May; Vol. 143 (5), pp. 790-800.e12. Date of Electronic Publication: 2022 Dec 07.
DOI:	10.1016/j.jid.2022.10.019
Abstrakt:	FLG variants underlie ichthyosis vulgaris and increased risk of atopic dermatitis, conditions typified by disruption of the skin microbiome and cutaneous immune response. Yet, it remains unclear whether neonatal skin barrier compromise because of FLG deficiency alters the quality of commensal-specific T cells and the functional impact of such responses. To address these questions, we profiled changes in the skin barrier and early cutaneous immune response of neonatal C57BL/6 Flg ‒/‒ and wild-type mice using single-cell RNA sequencing, flow cytometry, and other modalities. Flg ‒/‒ neonates showed little alteration in transepidermal water loss or lipid- or corneocyte-related gene expression. However, they showed increases in barrier disruption genes, epidermal dye penetration, and numbers of skin CD4 + T cells. Using an engineered strain of Staphylococcus epidermidis (S. epidermidis 2W) to study the response to neonatal skin colonization, we found that commensal-specific CD4 + T cells were skewed in Flg ‒/‒ pups toward effector rather than regulatory T cells. This altered response persisted into adulthood, where it was typified by T helper 17 (Th17) cells and associated with increased susceptibility to imiquimod-induced skin inflammation. Thus, subtle but impactful differences in neonatal barrier function in Flg ‒/‒ mice are accompanied by a skewed commensal-specific CD4 + response, with enduring consequences for skin immune homeostasis. (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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