| Title: |
Role of Peptidyl Arginine Deiminase 4–Dependent Macrophage Extracellular Trap Formation in Type 1 Diabetes Pathogenesis. |
| Authors: |
Shen, Yiming, Shi, Ruiya, Lu, ShiPing, Wang, Yan, Zhou, Ziqi, Wu, Chenhua, You, Qi, Fan, Hongye, Wu, Jie |
| Source: |
Diabetes; Nov2024, Vol. 73 Issue 11, p1862-1874, 13p |
| Subject Terms: |
ARGININE deiminase, TYPE 1 diabetes, GENE expression, T cells, AUTOIMMUNE diseases |
| Abstract: |
Excessive formation of macrophage extracellular trap (MET) has been implicated in several autoimmune disease pathogeneses; however, its impact on type 1 diabetes (T1D) and related mechanisms remains enigmatic. We demonstrated the pivotal role of peptidyl arginine deiminase 4 (PAD4) in driving profuse MET formation and macrophage M1 polarization in intestinal inflammation in NOD mice. Genetic knockout of PAD4 or adoptive transfer of METs altered the proportion of proinflammatory T cells in the intestine, subsequently influencing their migration to the pancreas. Combining RNA sequencing and CUT&Tag analysis, we found activated PAD4 transcriptionally regulated CXCL10 expression. This study comprehensively investigated how excessive PAD4-mediated MET formation in the colon increases the aggravation of intestinal inflammation and proinflammatory T-cell migration and finally is involved in T1D progression, suggesting that inhibition of MET formation may be a potential therapeutic target in T1D. Article Highlights: The role of macrophage extracellular trap (MET) formation in the pathology of type 1 diabetes (T1D) remains unclear. We aimed to investigate the impact of MET formation on intestinal inflammation and its subsequent effect on the pathogenesis of T1D in NOD mice. Activated peptidyl arginine deiminase 4 (PAD4) facilitates MET formation and transcriptionally regulates CXCL10 expression, leading to accelerated T1D through the activation and migration of proinflammatory T cells via the gut/pancreas axis. Findings suggest that targeting PAD4-mediated MET formation could emerge as a potential therapeutic strategy. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
