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 G. Laing, Pierre Vantourout, Philip East, Takeshi Nitta, Tomoya Narita, Hiroshi Takayanagi, Regina Feederle and Adrian Hayday ()
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Anett Jandke: The Francis Crick Institute
Daisy Melandri: The Francis Crick Institute
Leticia Monin: The Francis Crick Institute
Dmitry S. Ushakov: The Francis Crick Institute
Adam G. Laing: The Francis Crick Institute
Pierre Vantourout: The Francis Crick Institute
Philip East: The Francis Crick Institute
Takeshi Nitta: University of Tokyo
Tomoya Narita: Musashino University
Hiroshi Takayanagi: University of Tokyo
Regina Feederle: Helmholtz Zentrum, München, German Research Centre for Environmental Health
Adrian Hayday: The Francis Crick Institute

Nature Communications, 2020, vol. 11, issue 1, 1-16

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.

Date: 2020
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DOI: 10.1038/s41467-020-17557-y

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