Nayrac M, Requena M, Loiseau C, et al. - In most HIV-1-infected individuals on antiretroviral therapy, gut CD4+ T cells are incompletely restored notably Th17 cells, a key subset in mucosal homeostasis, but gut Th22 cells are usually restored at normal frequencies. Th22 cells exhibit a CCR6+CCR10+ phenotype and could thus respond to CCL20- and CCL28-mediated chemotaxis, while Th17 cells, which express CCR6 but not CCR10, depend on CCL20. In this study, duodenal enterocytes of treated HIV-1-infected individuals normally expressed CCL28, while bluntly expressed CCL20. In ex vivo study, Th22 cells were identified contributing to the decease in CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Migration of Th22 cells preferentially involves CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, Th22 cells can migrate via the CCR10–CCL28 axis, as an alternative to CCR6–CCL20 when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals. This could provide explanation to the better reconstitution of gut Th22 compared with Th17 cells in response to antiretroviral therapy. Lastly, the correlation between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation was assessed, revealing that Th22 cells do not compensate for the loss of Th17 cells in HIV-1-infected individuals on antiretroviral therapy.