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CCR6− regulatory T cells blunt the restoration of gut Th17 cells along the CCR6–CCL20 axis in treated HIV-1-infected individuals
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CCR6− regulatory T cells blunt the restoration of gut Th17 cells along the CCR6–CCL20 axis in treated HIV-1-infected individuals
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Journal Article
CCR6− regulatory T cells blunt the restoration of gut Th17 cells along the CCR6–CCL20 axis in treated HIV-1-infected individuals
2016
Overview
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.
Publisher
Elsevier Inc,Nature Publishing Group US,Elsevier Limited,Nature Pub. Group
Subject
/ Adult
/ Anti-HIV Agents - therapeutic use
/ Antiretroviral Therapy, Highly Active
/ Biomedical and Life Sciences
/ Chemokine CCL20 - immunology
/ Female
/ Forkhead Transcription Factors - genetics
/ Forkhead Transcription Factors - immunology
/ HIV Infections - drug therapy
/ HIV-1 - growth & development
/ Humans
/ Intestinal Mucosa - drug effects
/ Intestinal Mucosa - immunology
/ Intestinal Mucosa - virology
/ Intestine, Small - drug effects
/ Intestine, Small - immunology
/ Male
/ Receptors, CCR6 - deficiency
/ Receptors, CCR6 - immunology
/ T-Lymphocytes, Regulatory - drug effects
/ T-Lymphocytes, Regulatory - immunology
/ T-Lymphocytes, Regulatory - virology
