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 GuandaliniAaron R. Dinner, Sonia S. Kupfer, Hugh H. Reid, Luis B. Barreiro, Jamie Rossjohn, David A. Price, Bana Jabri

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


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: Chronic inflammation, driven in the context of celiac disease by persistent antigenic challenge with dietary gluten, permanently reshapes the tissue-resident innate-like TCRγδ+ intraepithelial lymphocyte compartment.

Original languageEnglish
Pages (from-to)967-981.e19
Issue number5
StatePublished - 21 Feb 2019
Externally publishedYes


  • butyrophilin-like molecules
  • celiac disease
  • intraepithelial lymphocytes
  • tissue-resident lymphocytes
  • γδ T cells


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