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Mucosal Immunol. 2016 Sep;9(5):1137-50. doi: 10.1038/mi.2016.7. Epub 2016 Feb 17.

CCR6(-) regulatory T cells blunt the restoration of gut Th17 cells along the CCR6-CCL20 axis in treated HIV-1-infected individuals.

Author information

1
INSERM, UMR1043, Toulouse, France.
2
CHU de Toulouse, Laboratoire de Virologie, Toulouse, France.
3
Emory Vaccine Center and Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
4
Université Toulouse III Paul Sabatier, Toulouse, France.
5
CHU de Toulouse, Service de Chirurgie Générale et Digestive, Toulouse, France.
6
CHU de Toulouse, Service de Gastro-Entérologie et Hépatologie-Pôle Digestif, Toulouse, France.
7
CHU de Toulouse, Service de Médecine Interne-Pôle Digestif, Toulouse, France.
8
IRD UMR152, Toulouse, France.
9
CHU de Toulouse, Service des Maladies Infectieuses et Tropicales, Toulouse, France.

Abstract

The gut CD4(+) T cells, particularly the T helper type 17 (Th17) subset, are not completely restored in most HIV-1-infected individuals despite combined antiretroviral therapy, when initiated at the chronic phase of infection. We show here that the CCR6-CCL20 chemotactic axis is altered, with reduced CCL20 production by small intestine epithelial cells in treated HIV-1-infected individuals. This leads to impaired CCR6(+)CD4(+) T-cell homing, particularly Th17 cells, to the small intestine mucosa. In contrast, the frequency of gut FoxP3(+) T regulatory (Treg) cells, specifically the CCR6(-) subset, was increased. The resulting imbalance in the Th17/CCR6(-) Treg ratio and the associated shift from interleukin (IL)-17 to IL-10 and transforming growth factor-β (TGF-β) blunts CCL20 production by enterocytes, perpetuating a negative feedback for the recruitment of CCR6(+)CD4(+) T cells to the small intestine in treated HIV-1-infected individuals.

PMID:
26883727
DOI:
10.1038/mi.2016.7
[Indexed for MEDLINE]

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