Profound Defect of Amphiregulin Secretion by Regulatory T Cells in the Gut of HIV-Treated Patients

Abstract

The persistence of a leaky gut in HIV-treated patients leads to chronic inflammation with increased rates of cardiovascular, liver, kidney, and neurological diseases. Tissue regulatory T (tTreg) cells are involved in the maintenance of intestinal homeostasis and wound repair through the IL-33 pathway. In this study, we investigated whether the persistence of gut mucosal injury during HIV infection might be explained in part by a flaw in the mechanisms involved in tissue repair. We observed an increased level of IL-33 in the gut of HIV-infected patients, which is associated with an increased level of fibrosis and a low peripheral reconstitution of CD4+ T cells. Our results showed that intestinal Treg cells from HIV-infected patients were enriched in tTreg cells prone to support tissue repair. However, we observed a functional defect in tTreg cells caused by the lack of amphiregulin secretion, which could contribute to the maintenance of intestinal damage. Our data suggest a mechanism by which the lack of amphiregulin secretion by tTreg may contribute to the lack of repair of the epithelial barrier.

Tissue damage during acuteTrypanosoma cruziinfection is associated with reduced reparative regulatory T cell response and can be attenuated by early interleukin-33 administration

“…Additionally, trTregs increased in the liver during S. japonicum helminth infection, where they significantly ameliorated tissue pathology [21]. In contrast, ST2+ Tregs that accumulated in the intestinal lamina propria of chronically HIV-infected patients had a limited role in tissue repair, as these individuals exhibited heightened epithelial permeability and tissue fibrosis [22]. In protozoan infections, different roles for trTregs have been reported, with their protective function noted in cerebral malaria [23], while their relevance in SM pathology during toxoplasmosis appeared negligible [24].…”

“…No reuse allowed without permission. a limited role in tissue repair, as these individuals exhibited heightened epithelial permeability and tissue fibrosis [22]. In protozoan infections, different roles for trTregs have been reported, with their protective function noted in cerebral malaria [23], while their relevance in SM pathology during toxoplasmosis appeared negligible [24].…”

Urinary α 1-microglobulin and β 2-microglobulin as markers of early kidney injury in HIV-positive male patients on tenofovir-based antiretroviral therapy

“…The toxicity of TDF is well-known for its involvement in the proximal renal tubules. Meanwhile, the estimated glomerular filtration rate (eGFR) has traditionally served as a means to assess the glomerular function in individuals, playing a crucial role as a functional index in diagnosing and staging chronic kidney disease (CKD) [9,10]. Biomarkers indicating tubular pathology have been demonstrated to be more sensitive compared to eGFR detection as tubular dysfunction often precedes the decline in eGFR [11][12][13][14][15].…”