posted on 2020-08-05, 17:03authored byAnett Jandke, Daisy Melandri, Leticia Monin, Dmitry S Ushakov, Adam G Laing, Pierre Vantourout, Philip East, Takeshi Nitta, Tomoya Narita, Hiroshi Takayanagi, Regina Feederle, Adrian Hayday
Butyrophilin-like (Btnl) genes are emerging as major epithelial determinants of tissue-associated γδ T cell compartments. Thus, the development of signature, murine TCRγδ+ intraepithelial lymphocytes (IEL) in gut and skin depends on Btnl family members, Btnl1 and Skint1, respectively. In seeking mechanisms underlying these profound effects, we now show that normal gut and skin γδ IEL development additionally requires Btnl6 and Skint2, respectively, and furthermore that different Btnl heteromers can seemingly shape different intestinal γδ+ IEL repertoires. This formal genetic evidence for the importance of Btnl heteromers also applied to the steady-state, since sustained Btnl expression is required to maintain the signature TCR.Vγ7+ IEL phenotype, including specific responsiveness to Btnl proteins. In sum, Btnl proteins are required to select and to maintain the phenotypes of tissue-protective γδ IEL compartments, with combinatorially diverse heteromers having differential impacts on different IEL subsets.
Funding
Crick (Grant ID: 10093, Grant title: Hayday FC001093)
European Commission (Grant ID: 792383 - UTERUS, Grant title: EC 792383 - UTERUS)