| Title: |
IL‐4/STAT6‐signaling Influences Local Inflammation and Regeneration Processes During Acute Pancreatitis and Promotes Fibrosis by a Direct Activation of Pancreatic Fibroblasts During Chronic Pancreatitis. |
| Authors: |
ElSheikh, Hager; Salvers, Annika; Piesker, Judith; Buchholz, Shenja; Lange, Rabea; Ameling, Sabine; Steil, Leif; Hammer, Elke; Homuth, Georg; Völker, Uwe; Bröker, Barbara M.; Weiss, Frank U.; Sendler, Matthias; Glaubitz, Juliane |
| Source: |
Advanced Science; 3/9/2026, Vol. 13 Issue 14, p1-21, 21p |
| Subject Terms: |
PANCREATITIS; CHRONIC pancreatitis; FIBROBLASTS; FIBROSIS; INTERLEUKIN-1; INFLAMMATION; JAK-STAT pathway; IMMUNE response |
| Abstract: |
In both acute and chronic pancreatitis, the local pancreatic immune response has a significant influence on the course of the disease. Utilizing a murine model deficient in STAT6, we demonstrate that the IL‐4/IL‐13/STAT6‐signaling pathway, which is a central component of the type 2 immune response, is rapidly activated during acute pancreatitis, thereby suppressing the pro‐inflammatory reaction and dampening the inflammation‐driven disease severity. The deletion of STAT6 in Stat6‐/‐ knock‐out mice surprisingly do not affect the numbers of CD206+ macrophages nor the release of TGF‐β. Notably, Stat6‐/‐ macrophages in CP are characterized by a high expression of the M2 markers Fizz1, Ym1 and Arg1, but also showed pro‐inflammatory properties, indicated by the expression of Nos2, Il1b and Mmp9. This mixed functional phenotype corresponded to a prolonged pro‐inflammatory response in pancreatitis and an impairment of acinar cell regeneration. STAT6‐signaling directly stimulated the production of selected extracellular matrix components in pancreatitis associated fibroblasts (PAFs). However, deletion of STAT6 only moderately reduced the fibrosis during chronic pancreatitis. Our study demonstrates that the IL‐4/IL‐13 STAT6‐signaling pathway represents a critical regulatory mechanism suppressing the inflammation and stimulating wound healing and organ regeneration during acute and chronic pancreatitis. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |