Journal
MUCOSAL IMMUNOLOGY
Volume 14, Issue 1, Pages 219-228Publisher
ELSEVIER SCIENCE INC
DOI: 10.1038/s41385-020-0286-6
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Funding
- Agence Nationale de Recherches sur le Sida et les Hepatites Virales (ANRS EP61 GALT study)
- Sidaction
- Institut Universitaire de France
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In individuals infected with HIV-1 and receiving antiretroviral therapy, gut Th22 cells are better restored compared to Th17 cells, potentially due to their mechanism of reducing CCL20 production in enterocytes through IL-22 and IL-18. When the ratio of CCL20/CCL28 decreases, Th22 cells can migrate via the CCR10-CCL28 axis as an alternative pathway.
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.
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