Deficient resident memory T-cell and CD8 T-cell response to commensals in inflammatory bowel disease

Noble, A., Durant, L., Hoyles, L. ORCID: 0000-0002-6418-342X, McCartney, A.L., Man, R., Segal, J., Costello, S.P., Hendy, P., Reddi, D., Bouri, S., Lim, D.N.F., Pring, T., O'Connor, M.J., Datt, P., Wilson, A., Arebi, N., Akbar, A., Hart, A.L., Carding, S.R. and Knight, S.C., 2019. Deficient resident memory T-cell and CD8 T-cell response to commensals in inflammatory bowel disease. Journal of Crohn's and Colitis. ISSN 1873-9946

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Abstract

Background & Aims: The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease (IBD).

Methods: Resident memory T-cells (Trm) in colonic biopsies and local antibody responses to intraepithelial microbes were analyzed. Systemic antigen-specific immune T- and B-cell memory to a panel of commensal microbes was assessed.

Results: Systemically, healthy blood showed CD4 and occasional CD8 memory T-cell responses to selected intestinal bacteria but few memory B-cell responses. In IBD, CD8 memory T-cell responses decreased although B-cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T-cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T-cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T-cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T-cell function via CD39. Cognate interaction between T-cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses.

Conclusions: A previously unrecognized imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T-cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells rather than immunosuppression may reinforce tissue immunity, improve barrier function and prevent B-cell dysfunction in microbiota-associated disease and IBD etiology.

Item Type:	Journal article
Alternative Title:	Deficient resident memory T-cells in IBD [short title]
Publication Title:	Journal of Crohn's and Colitis
Creators:	Noble, A., Durant, L., Hoyles, L., McCartney, A.L., Man, R., Segal, J., Costello, S.P., Hendy, P., Reddi, D., Bouri, S., Lim, D.N.F., Pring, T., O'Connor, M.J., Datt, P., Wilson, A., Arebi, N., Akbar, A., Hart, A.L., Carding, S.R. and Knight, S.C.
Publisher:	Oxford University Press
Date:	26 October 2019
ISSN:	1873-9946
Identifiers:	Number Type 10.1093/ecco-jcc/jjz175 DOI 1120765 Other
Divisions:	Schools > School of Science and Technology
Record created by:	Linda Sullivan
Date Added:	03 Oct 2019 13:31
Last Modified:	31 Oct 2019 10:58
URI:	https://irep.ntu.ac.uk/id/eprint/37899

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