Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease

Toufic Mayassi; Kristin Ladell; Herman Gudjonson; James E McLaren; Dustin G Shaw; Mai T Tran; Jagoda J Rokicka; Ian Lawrence; Jean-Christophe Grenier; Vincent van Unen; Cezary Ciszewski; Matthew Dimaano; Hoda E Sayegh; Vinod Kumar; Cisca Wijmenga; Peter H R Green; Ranjana Gokhale; Hilary Jericho; Carol E Semrad; Stefano Guandalini; Aaron R Dinner; Sonia S Kupfer; Hugh H Reid; Luis B Barreiro; Jamie Rossjohn; David A Price; Bana Jabri

doi:10.1016/j.cell.2018.12.039

Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease

Cell. 2019 Feb 21;176(5):967-981.e19. doi: 10.1016/j.cell.2018.12.039. Epub 2019 Feb 7.

Authors

Toufic Mayassi¹, Kristin Ladell², Herman Gudjonson³, James E McLaren², Dustin G Shaw¹, Mai T Tran⁴, Jagoda J Rokicka⁵, Ian Lawrence⁵, Jean-Christophe Grenier⁶, Vincent van Unen⁷, Cezary Ciszewski⁵, Matthew Dimaano⁵, Hoda E Sayegh⁵, Vinod Kumar⁸, Cisca Wijmenga⁸, Peter H R Green⁹, Ranjana Gokhale¹⁰, Hilary Jericho¹⁰, Carol E Semrad¹¹, Stefano Guandalini¹⁰, Aaron R Dinner¹², Sonia S Kupfer¹³, Hugh H Reid¹⁴, Luis B Barreiro⁶, Jamie Rossjohn¹⁵, David A Price¹⁶, Bana Jabri¹⁷

Affiliations

¹ Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA.
² Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK.
³ Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA; Department of Chemistry, University of Chicago, Chicago, IL, USA.
⁴ Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia.
⁵ Department of Medicine, University of Chicago, Chicago, IL, USA.
⁶ Department of Genetics, CHU Sainte-Justine Research Center, Montreal, QC, Canada.
⁷ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, the Netherlands.
⁸ Department of Genetics, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
⁹ Celiac Disease Center, College of Physicians and Surgeons, Columbia University Medical Center, New York, NY, USA.
¹⁰ Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.
¹¹ Department of Medicine, University of Chicago, Chicago, IL, USA; University of Chicago Celiac Disease Center, University of Chicago, Chicago, IL, USA.
¹² Institute for Biophysical Dynamics, University of Chicago, Chicago, IL, USA; Department of Chemistry, University of Chicago, Chicago, IL, USA; James Franck Institute, University of Chicago, Chicago, IL, USA.
¹³ Department of Medicine, University of Chicago, Chicago, IL, USA; Section of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, University of Chicago, Chicago, IL, USA.
¹⁴ Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia.
¹⁵ Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK; Infection and Immunity Program and Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia; Australian Research Council Centre of Excellence in Advanced Molecular Imaging, Monash University, Clayton, VIC, Australia.
¹⁶ Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff, UK. Electronic address: priced6@cardiff.ac.uk.
¹⁷ Committee on Immunology, University of Chicago, Chicago, IL, USA; Department of Medicine, University of Chicago, Chicago, IL, USA; Department of Pathology, University of Chicago, Chicago, IL, USA. Electronic address: bjabri@bsd.uchicago.edu.

Abstract

Tissue-resident lymphocytes play a key role in immune surveillance, but it remains unclear how these inherently stable cell populations respond to chronic inflammation. In the setting of celiac disease (CeD), where exposure to dietary antigen can be controlled, gluten-induced inflammation triggered a profound depletion of naturally occurring Vγ4⁺/Vδ1⁺ intraepithelial lymphocytes (IELs) with innate cytolytic properties and specificity for the butyrophilin-like (BTNL) molecules BTNL3/BTNL8. Creation of a new niche with reduced expression of BTNL8 and loss of Vγ4⁺/Vδ1⁺ IELs was accompanied by the expansion of gluten-sensitive, interferon-γ-producing Vδ1⁺ IELs bearing T cell receptors (TCRs) with a shared non-germline-encoded motif that failed to recognize BTNL3/BTNL8. Exclusion of dietary gluten restored BTNL8 expression but was insufficient to reconstitute the physiological Vγ4⁺/Vδ1⁺ subset among TCRγδ⁺ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRγδ⁺ IEL compartment in CeD. VIDEO ABSTRACT.

Keywords: butyrophilin-like molecules; celiac disease; intraepithelial lymphocytes; tissue-resident lymphocytes; γδ T cells.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antigens
Butyrophilins / metabolism
Celiac Disease / immunology*
Celiac Disease / physiopathology
Chronic Disease
Diet, Gluten-Free
Glutens / metabolism
HEK293 Cells
Humans
Inflammation / immunology*
Inflammation / metabolism
Intestinal Mucosa / immunology
Intraepithelial Lymphocytes / immunology
Intraepithelial Lymphocytes / metabolism
Receptors, Antigen, T-Cell / immunology
Receptors, Antigen, T-Cell / metabolism
Receptors, Antigen, T-Cell, gamma-delta / immunology*
Receptors, Antigen, T-Cell, gamma-delta / metabolism

Substances

Antigens
Butyrophilins
Receptors, Antigen, T-Cell
Receptors, Antigen, T-Cell, gamma-delta
Glutens

Abstract

Publication types

MeSH terms

Substances

Grants and funding