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

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