Butyrophilin-like proteins display combinatorial diversity in selecting and maintaining signature intraepithelial γδ T cell compartments
Anett Jandke, Daisy Melandri, Leticia Monin, Dmitry S. Ushakov, Adam Laing, Pierre Vantourout, Philip East, Takeshi Nitta, Tomoya Narita, Hiroshi Takayanagi, Regina Feederle, Adrian Hayday
Abstract
Abstract 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.