PPARγ downregulation in colonic CD8+ T cells results in epithelial barrier disruption in people with HIV on antiretroviral therapy
Das Adhikari, U.; Froehle, L. M.; Pipkin, A. N.; Baharlou, H.; Linder, A. H.; Shah, P.; Hussey, A.; Zhang, Q.; Nyquist, S.; Khwaled, S.; Chi, F.; Goswami, S.; Dieffenbach, T. J.; Read, B. J.; Kim, B.; Irvine, D. J.; Asowata, O.; Ladinsky, M. S.; Bjorkman, P.; Madela, F.; Khader, S.; Shalek, A. K.; Ghebremichael, M.; Kloverpris, H.; Ringel, A.; Yilmaz, O. H.; Kwon, D. S.
Show abstract
A hallmark of HIV infection is disruption of intestinal barrier integrity that persists in people with HIV (PWH) despite treatment with antiretroviral therapy (ART). This disruption is central to HIV disease progression, yet the causes remain incompletely understood. We report a novel mechanism by which immunometabolic defects in colon resident CD8+ T cells in PWH lead to intestinal epithelial apoptosis and disruption of intestinal barrier integrity. We show that in PWH, these cells downregulate the lipid sensor peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}), which results in reduced intracellular lipid droplets, impaired fatty acid oxidation, and acquisition of lipids by CD8+ T cells from intestinal epithelial cells, which then contributes to epithelial cell death. Our findings indicate that HIV-associated immunometabolic dysregulation of colon CD8+ T cell leads to loss of intestinal epithelial homeostasis. These results identify potential new strategies to reduce comorbidities in PWH and other disorders with disrupted intestinal barrier integrity.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Intestinal epithelial MHC class II regulation by HDAC3 instructs microbiota-specific CD4+ T cells 96%
- A20's Linear Ubiquitin Binding Motif Restrains Pathogenic Activation of TH17/22 cells and IL-22 Driven Enteritis 96%
- Targeting Specific Kinase Substrates Rescues Increased Colitis Severity Induced by the Crohn's Disease-Linked LRRK2-N2081D Variant 96%
Similar papers in this journal
- The Septin Cytoskeleton is a Novel Regulator of Intestinal Epithelial Barrier Integrity and Mucosal Inflammation 96%
- MTG16 (CBFA2T3) regulates colonic epithelial differentiation, colitis, and tumorigenesis by repressing E protein transcription factors 96%
- Aberrant miR-29 is a predictive feature of severe phenotypes in pediatric Crohn's disease 95%
Similar papers in this journal
- Multiomic analysis reveals cellular and epigenetic plasticity in intestinal pouches of ulcerative colitis patients 96%
- Metformin enhances anti-mycobacterial responses by educating immunometabolic circuits of CD8+ T cells 96%
- Sprouty2 limits intestinal tuft and goblet cell numbers through GSK3β-mediated restriction of epithelial IL-33. 96%
Similar papers in this journal
- Microbiota promote enhanced CD39 expression in γδ intraepithelial lymphocytes through the activation of TCR and IL-15 signaling 96%
- MHC class II antigen presentation by intestinal epithelial cells fine-tunes bacteria-reactive CD4 T cell responses 96%
- A transmissible γδ intraepithelial lymphocyte hyperproliferative phenotype is associated with the intestinal microbiota and confers protection against acute infection. 96%
Similar papers in this journal
- Tongue immune compartment analysis reveals spatial macrophage heterogeneity 95%
- Phosphoglycerate mutase regulates Treg differentiation through control of serine synthesis and one-carbon metabolism 95%
- Sex-dependent gastrointestinal colonization resistance to MRSA is microbiota and Th17 dependent 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.