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

Panea, C, Zhang, R, VanValkenburgh, J, Ni, M, Adler, C, Wei, Y, Ochoa, F, Schmahl, J, Tang, Y, Siao, CJ, Poueymirou, W, Espert, J, Lim, WK, Atwal, GS, Murphy, AJ, Sleeman, MA, Hovhannisyan, Z, Haxhinasto, S (July 2021) Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes. Communications Biology, 4 (1). ISSN 2399-3642 (In Press)

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DOI: 10.1038/s42003-021-02438-x

Abstract

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.

Item Type: Paper
Subjects: organs, tissues, organelles, cell types and functions > tissues types and functions > epithelium
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > immune cell
CSHL Authors:
Communities: CSHL labs > Atwal lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 26 July 2021
Date Deposited: 11 Aug 2021 15:19
Last Modified: 18 Aug 2021 13:45
PMCID: PMC8313535
URI: https://repository.cshl.edu/id/eprint/40319

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