2. Academic Validation
  3. Butyrophilin-like proteins display combinatorial diversity in selecting and maintaining signature intraepithelial γδ T cell compartments

Butyrophilin-like proteins display combinatorial diversity in selecting and maintaining signature intraepithelial γδ T cell compartments

  • Nat Commun. 2020 Jul 28;11(1):3769. doi: 10.1038/s41467-020-17557-y.
Anett Jandke 1,  Daisy Melandri 1 2,  Leticia Monin 1,  Dmitry S Ushakov 1 2,  Adam G Laing 1 2,  Pierre Vantourout 1 2,  Philip East 3,  Takeshi Nitta 4,  Tomoya Narita 5,  Hiroshi Takayanagi 4,  Regina Feederle 6,  Adrian Hayday 7 8
Affiliations

Affiliations

  • 1 Immunosurveillance Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW11AT, UK.
  • 2 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London Bridge, London, SE19RT, UK.
  • 3 Bioinformatics and Biostatistics Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW11AT, UK.
  • 4 Department of Immunology, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan.
  • 5 Department of Pharmacotherapy, Research Institute of Pharmaceutical Sciences, Musashino University, Nishitokyo, Tokyo, 202-8585, Japan.
  • 6 Monoclonal Antibody Core Facility, Institute for Diabetes and Obesity, Helmholtz Zentrum, München, German Research Centre for Environmental Health, 85764, Neuherberg, Germany.
  • 7 Immunosurveillance Laboratory, The Francis Crick Institute, 1 Midland Road, London, NW11AT, UK. [email protected].
  • 8 Peter Gorer Department of Immunobiology, School of Immunology and Microbial Sciences, King's College London, Great Maze Pond, London Bridge, London, SE19RT, UK. [email protected].
PMID: 32724083 DOI: 10.1038/s41467-020-17557-y
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.

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