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Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes

Tissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR(+) IELs, however, the mechanisms that cont...

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Autores principales: Panea, Casandra, Zhang, Ruoyu, VanValkenburgh, Jeffrey, Ni, Min, Adler, Christina, Wei, Yi, Ochoa, Francisca, Schmahl, Jennifer, Tang, Yajun, Siao, Chia-Jen, Poueymirou, William, Espert, Jennifer, Lim, Wei Keat, Atwal, Gurinder S., Murphy, Andrew J., Sleeman, Matthew A., Hovhannisyan, Zaruhi, Haxhinasto, Sokol
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313535/
https://www.ncbi.nlm.nih.gov/pubmed/34312491
http://dx.doi.org/10.1038/s42003-021-02438-x
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author Panea, Casandra
Zhang, Ruoyu
VanValkenburgh, Jeffrey
Ni, Min
Adler, Christina
Wei, Yi
Ochoa, Francisca
Schmahl, Jennifer
Tang, Yajun
Siao, Chia-Jen
Poueymirou, William
Espert, Jennifer
Lim, Wei Keat
Atwal, Gurinder S.
Murphy, Andrew J.
Sleeman, Matthew A.
Hovhannisyan, Zaruhi
Haxhinasto, Sokol
author_facet Panea, Casandra
Zhang, Ruoyu
VanValkenburgh, Jeffrey
Ni, Min
Adler, Christina
Wei, Yi
Ochoa, Francisca
Schmahl, Jennifer
Tang, Yajun
Siao, Chia-Jen
Poueymirou, William
Espert, Jennifer
Lim, Wei Keat
Atwal, Gurinder S.
Murphy, Andrew J.
Sleeman, Matthew A.
Hovhannisyan, Zaruhi
Haxhinasto, Sokol
author_sort Panea, Casandra
collection PubMed
description Tissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR(+) IELs, however, the mechanisms that control γδ IEL maintenance within discrete intestinal segments are unclear. Here, we show that Btnl2 suppressed homeostatic proliferation of γδ IELs preferentially in the ileum. High throughput transcriptomic characterization of site-specific Btnl2-KO γδ IELs reveals that Btnl2 regulated the antimicrobial response module of ileal γδ IELs. Btnl2 deficiency shapes the TCR specificities and TCRγ/δ repertoire diversity of ileal γδ IELs. During DSS-induced colitis, Btnl2-KO mice exhibit increased inflammation and delayed mucosal repair in the colon. Collectively, these data suggest that Btnl2 fine-tunes γδ IEL frequencies and TCR specificities in response to site-specific homeostatic and inflammatory cues. Hence, Btnl-mediated targeting of γδ IEL development and maintenance may help dissect their immunological functions in intestinal diseases with segment-specific manifestations.
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spelling pubmed-83135352021-08-03 Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes Panea, Casandra Zhang, Ruoyu VanValkenburgh, Jeffrey Ni, Min Adler, Christina Wei, Yi Ochoa, Francisca Schmahl, Jennifer Tang, Yajun Siao, Chia-Jen Poueymirou, William Espert, Jennifer Lim, Wei Keat Atwal, Gurinder S. Murphy, Andrew J. Sleeman, Matthew A. Hovhannisyan, Zaruhi Haxhinasto, Sokol Commun Biol Article Tissue-resident γδ intraepithelial lymphocytes (IELs) orchestrate innate and adaptive immune responses to maintain intestinal epithelial barrier integrity. Epithelia-specific butyrophilin-like (Btnl) molecules induce perinatal development of distinct Vγ TCR(+) IELs, however, the mechanisms that control γδ IEL maintenance within discrete intestinal segments are unclear. Here, we show that Btnl2 suppressed homeostatic proliferation of γδ IELs preferentially in the ileum. High throughput transcriptomic characterization of site-specific Btnl2-KO γδ IELs reveals that Btnl2 regulated the antimicrobial response module of ileal γδ IELs. Btnl2 deficiency shapes the TCR specificities and TCRγ/δ repertoire diversity of ileal γδ IELs. During DSS-induced colitis, Btnl2-KO mice exhibit increased inflammation and delayed mucosal repair in the colon. Collectively, these data suggest that Btnl2 fine-tunes γδ IEL frequencies and TCR specificities in response to site-specific homeostatic and inflammatory cues. Hence, Btnl-mediated targeting of γδ IEL development and maintenance may help dissect their immunological functions in intestinal diseases with segment-specific manifestations. Nature Publishing Group UK 2021-07-26 /pmc/articles/PMC8313535/ /pubmed/34312491 http://dx.doi.org/10.1038/s42003-021-02438-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Panea, Casandra
Zhang, Ruoyu
VanValkenburgh, Jeffrey
Ni, Min
Adler, Christina
Wei, Yi
Ochoa, Francisca
Schmahl, Jennifer
Tang, Yajun
Siao, Chia-Jen
Poueymirou, William
Espert, Jennifer
Lim, Wei Keat
Atwal, Gurinder S.
Murphy, Andrew J.
Sleeman, Matthew A.
Hovhannisyan, Zaruhi
Haxhinasto, Sokol
Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title_full Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title_fullStr Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title_full_unstemmed Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title_short Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
title_sort butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313535/
https://www.ncbi.nlm.nih.gov/pubmed/34312491
http://dx.doi.org/10.1038/s42003-021-02438-x
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