Increase of CXCR3+ T cells impairs Th17 cells recruitment in the small intestine mucosa through IFN-g and IL-18 during treated HIV-1 infection

Loiseau, C., Requena, M., Nayrac, M., Mavigner, M., Cazabat, M., Iscache, A.L., Carrere, N., Suc, B., Alric, L., Izopet, J., and Delobel, P. (2019) Increase of CXCR3+ T cells impairs Th17 cells recruitment in the small intestine mucosa through IFN-g and IL-18 during treated HIV-1 infection. Journal of Infectious Diseases, 220 (5). pp. 830-840.

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View at Publisher Website: https://doi.org/10.1093/infdis/jiz123
 
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Abstract

The restoration of CD4+ T cells, especially T-helper type 17 (Th17) cells, remains incomplete in the gut mucosa of most human immunodeficiency virus type 1 (HIV-1)–infected individuals despite sustained antiretroviral therapy (ART). Herein, we report an increase in the absolute number of CXCR3+ T cells in the duodenal mucosa during ART. The frequencies of Th1 and CXCR3+ CD8+ T cells were increased and negatively correlated with CCL20 and CCL25 expression in the mucosa. In ex vivo analyses, we showed that interferon γ, the main cytokine produced by Th1 and effector CD8+ T cells, downregulates the expression of CCL20 and CCL25 by small intestine enterocytes, while it increases the expression of CXCL9/10/11, the ligands of CXCR3. Interleukin 18, a pro-Th1 cytokine produced by enterocytes, also contributes to the downregulation of CCL20 expression and increases interferon γ production by Th1 cells. This could perpetuate an amplification loop for CXCR3-driven Th1 and effector CD8+ T cells recruitment to the gut, while impairing Th17 cells homing through the CCR6-CCL20 axis in treated HIV-1–infected individuals.

Item ID: 57869
Item Type: Article (Research - C1)
ISSN: 1537-6613
Keywords: HIV-1, gut, CXCR3, Th1, CD8, IFN-γ, IL-18, CCL20, CCL25
Copyright Information: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
Funders: Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS), Sidaction
Date Deposited: 02 Sep 2019 23:06
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110799 Immunology not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 50%
92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 50%
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