Increased angiopoietin-like 4 expression ameliorates inflammatory bowel diseases via suppressing CD8+ T cell activities.

Abstract

Angiopoietin-like 4 (ANGPTL4) is involved in inflammation-associated diseases, such as rheumatoid arthritis, type 2 diabetes, atherosclerosis, and chronic obstructive pulmonary disease. The role of ANGPTL4 in the pathogenesis of inflammatory bowel disease (IBD) remains unknown. Here, the plasma ANGPTL4 levels peaked on days 3 and 5, and expression of ANGPTL4 of inflamed colons peaked on days 5 and 7 in mice with dextran sulfate sodium (DSS)-induced colitis. Simultaneously, CD8+T cells in the inflamed colons peaked at day 5 but declined at day 7. However, the ANGPTL4-/- mice treated with DSS exhibited exacerbated colitis with more CD8+T cells and macrophages infiltrating the colons. The exogenous ANGPTL4 protein protected the mice against DSS-induced colitis with less CD8+T cell and macrophage recruitment in the colons. In addition, recombinant ANGPTL4 directly downregulated the IFN-γ and NKG2D expression of CD8+T cells but had no effects on the CD86 expression and TNF-α secretion of macrophages ex vivo. Adding ANGPTL4 protein into ANGPTL4-/- mice almost blocked the onset of DSS-induced colitis. In parallel, the plasma ANGPTL4 levels were elevated in patients with Crohn's disease and ulcerative colitis at mild/moderate stage and restored to normal levels in IBD patients at a severe stage. The higher ANGPTL4 expression in the inflamed colons of patients with IBD was correlated with lower CD8+ cell infiltration, whereas no associations with macrophages. Our results demonstrated the compensatory protective effect of ANGPTL4 on IBD development at least via the downregulation of CD8+T cell activities. Adding the ANGPTL4 protein would have beneficial effects to retard the progression of IBD.

• Authors: Xiaoyuan Zhang, Jing Tu, Shizhen Ding, Mei Wang, Yanbing Ding, Zhijie Lin, Guotao Lu, Weiming Xiao, Weijuan Gong
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 612 Pg. 37-43 (07 05 2022) ISSN: 1090-2104 [Electronic] United States
• PMID: 35500440 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2022. Published by Elsevier Inc.

Chemical References

• Angiopoietin-Like Protein 4
• Angiopoietins
• Dextran Sulfate

Topics

• Angiopoietin-Like Protein 4 (genetics)
• Angiopoietins (metabolism)
• Animals
• CD8-Positive T-Lymphocytes (metabolism)
• Colitis (chemically induced)
• Colon (pathology)
• Dextran Sulfate
• Diabetes Mellitus, Type 2 (metabolism)
• Disease Models, Animal
• Humans
• Inflammatory Bowel Diseases (pathology)
• Mice
• Mice, Inbred C57BL