Th22 cells are efficiently recruited in the gut by CCL28 as an alternative to CCL20 but do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals

Nayrac, Manon, Requena, Mary, Loiseau, Claire, Cazabat, Michelle, Suc, Bertrand, Carrere, Nicolas, Barange, Karl, Alric, Laurent, Martin-Blondel, Guillaume, Izopet, Jacques, and Delobel, Pierre (2020) Th22 cells are efficiently recruited in the gut by CCL28 as an alternative to CCL20 but do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals. Mucosal Immunology, 14. pp. 219-228.

[img] PDF (Published Version) - Published Version
Restricted to Repository staff only

View at Publisher Website: https://doi.org/10.1038/s41385-020-0286-...
 
2
2


Abstract

Gut CD4+ T cells are incompletely restored in most HIV-1-infected individuals on antiretroviral therapy, notably Th17 cells, a key subset in mucosal homeostasis. By contrast, gut Th22 cells are usually restored at normal frequencies. Th22 cells display 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. Herein, we found that CCL28 is normally expressed by duodenal enterocytes of treated HIV-1-infected individuals, while CCL20 expression is blunted. Ex vivo, we showed that Th22 cells contribute to the reduction of CCL20 production by enterocytes through an IL-22- and IL-18-dependent mechanism. Th22 cells preferentially migrate via CCL20- rather than CCL28-mediated chemotaxis when both chemokines are available in the microenvironment. However, when the CCL20/CCL28 ratio drops, as in treated HIV-1-infected individuals, Th22 cells can migrate via the CCR10–CCL28 axis, as an alternative to CCR6–CCL20. This could explain the better reconstitution of gut Th22 compared with Th17 cells on antiretroviral therapy. Lastly, we assessed the relationships between the frequencies of gut Th17 and Th22 cells and inflammatory markers related to microbial translocation, and showed that Th22 cells do not compensate for the loss of Th17 cells in treated HIV-1-infected individuals.

Item ID: 63210
Item Type: Article (Research - C1)
ISSN: 1935-3456
Keywords: HIV; Th22; Th17; gut; T cells; homing
Copyright Information: © Society for Mucosal Immunology 2020.
Date Deposited: 20 May 2020 07:48
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1103 Clinical Sciences > 110309 Infectious Diseases @ 50%
11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110704 Cellular Immunology @ 50%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920109 Infectious Diseases @ 100%
Downloads: Total: 2
Last 12 Months: 2
More Statistics

Actions (Repository Staff Only)

Item Control Page Item Control Page