Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease
Publication year
2019Author(s)
Source
Cell, 176, 5, (2019), pp. 967-981.e19ISSN
Publication type
Article / Letter to editor

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Organization
Internal Medicine
Journal title
Cell
Volume
vol. 176
Issue
iss. 5
Page start
p. 967
Page end
p. 981.e19
Subject
Radboudumc 4: lnfectious Diseases and Global Health RIMLS: Radboud Institute for Molecular Life SciencesAbstract
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 Vgamma4(+)/Vdelta1(+) 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 Vgamma4(+)/Vdelta1(+) IELs was accompanied by the expansion of gluten-sensitive, interferon-gamma-producing Vdelta1(+) 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 Vgamma4(+)/Vdelta1(+) subset among TCRgammadelta(+) IELs. Collectively, these data show that chronic inflammation permanently reconfigures the tissue-resident TCRgammadelta(+) IEL compartment in CeD. VIDEO ABSTRACT.
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- Academic publications [204024]
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- Faculty of Medical Sciences [80459]
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