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 & 7 others Aaron R. Dinner, Sonia S. Kupfer, Hugh H. Reid, Luis B. Barreiro, Jamie Rossjohn, David A. Price, Bana Jabri

Research output: Contribution to journalArticleResearchpeer-review

3 Citations (Scopus)

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: 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
Number of pages15
JournalCell
Volume176
Issue number5
DOIs
Publication statusPublished - 21 Feb 2019

Keywords

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

Cite this

Mayassi, T., Ladell, K., Gudjonson, H., McLaren, J. E., Shaw, D. G., Tran, M. T., ... Jabri, B. (2019). Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. Cell, 176(5), 967-981. https://doi.org/10.1016/j.cell.2018.12.039
Mayassi, Toufic ; Ladell, Kristin ; Gudjonson, Herman ; McLaren, James E. ; Shaw, Dustin G. ; Tran, Mai T. ; Rokicka, Jagoda J. ; Lawrence, Ian ; Grenier, Jean Christophe ; van Unen, Vincent ; Ciszewski, Cezary ; Dimaano, Matthew ; Sayegh, Hoda E. ; Kumar, Vinod ; Wijmenga, Cisca ; Green, Peter H.R. ; Gokhale, Ranjana ; Jericho, Hilary ; Semrad, Carol E. ; Guandalini, Stefano ; Dinner, Aaron R. ; Kupfer, Sonia S. ; Reid, Hugh H. ; Barreiro, Luis B. ; Rossjohn, Jamie ; Price, David A. ; Jabri, Bana. / Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. In: Cell. 2019 ; Vol. 176, No. 5. pp. 967-981.
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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: 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.",
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author = "Toufic Mayassi and Kristin Ladell and Herman Gudjonson and McLaren, {James E.} and Shaw, {Dustin G.} and Tran, {Mai T.} and Rokicka, {Jagoda J.} and Ian Lawrence and Grenier, {Jean Christophe} and {van Unen}, Vincent and Cezary Ciszewski and Matthew Dimaano and Sayegh, {Hoda E.} and Vinod Kumar and Cisca Wijmenga and Green, {Peter H.R.} and Ranjana Gokhale and Hilary Jericho and Semrad, {Carol E.} and Stefano Guandalini and Dinner, {Aaron R.} and Kupfer, {Sonia S.} and Reid, {Hugh H.} and Barreiro, {Luis B.} and Jamie Rossjohn and Price, {David A.} and Bana Jabri",
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Mayassi, T, Ladell, K, Gudjonson, H, McLaren, JE, Shaw, DG, Tran, MT, Rokicka, JJ, Lawrence, I, Grenier, JC, van Unen, V, Ciszewski, C, Dimaano, M, Sayegh, HE, Kumar, V, Wijmenga, C, Green, PHR, Gokhale, R, Jericho, H, Semrad, CE, Guandalini, S, Dinner, AR, Kupfer, SS, Reid, HH, Barreiro, LB, Rossjohn, J, Price, DA & Jabri, B 2019, 'Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease', Cell, vol. 176, no. 5, pp. 967-981. https://doi.org/10.1016/j.cell.2018.12.039

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

In: Cell, Vol. 176, No. 5, 21.02.2019, p. 967-981.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Mayassi, Toufic

AU - Ladell, Kristin

AU - Gudjonson, Herman

AU - McLaren, James E.

AU - Shaw, Dustin G.

AU - Tran, Mai T.

AU - Rokicka, Jagoda J.

AU - Lawrence, Ian

AU - Grenier, Jean Christophe

AU - van Unen, Vincent

AU - Ciszewski, Cezary

AU - Dimaano, Matthew

AU - Sayegh, Hoda E.

AU - Kumar, Vinod

AU - Wijmenga, Cisca

AU - Green, Peter H.R.

AU - Gokhale, Ranjana

AU - Jericho, Hilary

AU - Semrad, Carol E.

AU - Guandalini, Stefano

AU - Dinner, Aaron R.

AU - Kupfer, Sonia S.

AU - Reid, Hugh H.

AU - Barreiro, Luis B.

AU - Rossjohn, Jamie

AU - Price, David A.

AU - Jabri, Bana

PY - 2019/2/21

Y1 - 2019/2/21

N2 - 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.

AB - 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.

KW - butyrophilin-like molecules

KW - celiac disease

KW - intraepithelial lymphocytes

KW - tissue-resident lymphocytes

KW - γδ T cells

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Mayassi T, Ladell K, Gudjonson H, McLaren JE, Shaw DG, Tran MT et al. Chronic Inflammation Permanently Reshapes Tissue-Resident Immunity in Celiac Disease. Cell. 2019 Feb 21;176(5):967-981. https://doi.org/10.1016/j.cell.2018.12.039