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- Title
Butyrophilin-like 2 regulates site-specific adaptations of intestinal γδ intraepithelial lymphocytes.
- Authors
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
- 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. Panea et al showed that epithelia-specific butyrophilinlike 2 (Btnl2) suppressed homeostatic proliferation of γδ intraepithelial lymphocytes (IELs) preferentially in the ileum and used high throughput transcriptomic characterization of Btnl2-deficient γδ IELs to demonstrate that Btnl2 impacts γδ TCR specificities and repertoire diversity of ileal γδ IELs. In addition, they showed that Btnl2-deficient mice exhibited increased inflammation and delayed mucosal repair in the colon, suggesting that it plays a key immunological function in intestinal diseases.
- Subjects
BUTYROPHILIN; LYMPHOCYTES; IMMUNE response; TRANSCRIPTOMES; INTESTINAL diseases
- Publication
Communications Biology, 2021, Vol 4, Issue 1, p1
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-021-02438-x