Chronic inflammation permanently reshapes tissue-resident immunity in celiac disease

Author(s):
Mayassi, T.; Ladell, K.; Gudjonson, H.; McLaren, J.E.; Shaw, D.G.; Tran, M.T.; Rokicka, J.J.; Lawrence, I.; Grenier, J.C.; Unen, V. van (0000-0001-9339-8430); Ciszewski, C.; Dimaano, M.; Sayegh, H.E.; Kumar, V.; Wijmenga, C.; Green, P.H.R.; Gokhale, R.; Jericho, H.; Semrad, C.E.; Guandalini, S.; Dinner, A.R.; Kupfer, S.S.; Reid, H.H.; Barreiro, L.B.; Rossjohn, J.; Price, D.A.; Jabri, B.
Published
2019
Publication type
Article / Letter to editor

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 Vg4+ /Vd1+ 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 Vg4+ /Vd1+ IELs was accompanied by the expansion of gluten-sensitive, interferon-g-producing Vd1+ 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 Vg4+ /Vd1+ subset among TCRgd+ IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRgd+ IEL compartment in CeD.

Date issued
2019-02-21
Language
English
Is part of
Cell (2019), Vol. 176, no. 5, p. 967-+
hdl
1887/4094645
doi
10.1016/j.cell.2018.12.039