Japan Digestive Disease Week 2025
International Poster Session16 (JDDW)
October 31, 15:44–16:16, Room 15 (Kobe International Exhibition Hall No.1 Building Digital Poster Venue)
IP-81_G
Liver kinase B1 in CD11c+ macrophages inhibits fibrosis in chronic pancreatitis via the OSM-STAT3-CCL2/CCR2 axis
- 1
- Department of Gastroenterology, The Affiliated Hospital of Qingdao University
Objective:
Chronic pancreatitis (CP) is a progressive fibrotic disease and the treatment landscape remains highly unsatisfactory. This study aims to elucidate the role of Lkb1 in CD11c+ macrophages within the immune microenvironment and fibrosis of CP.
Design:
The expression of Lkb1 in CD11c+ cells was assessed in pancreatic tissues from CP patients. Additionally, CD11cCreLkb1f/f and Lkb1f/f mice were utilized to establish a cerulein-induced CP model. Single-cell RNA sequencing, flow cytometry, and immunofluorescence revealed changes in the pancreatic immune microenvironment.
Results:
This study explores the role of Lkb1 in regulating the immune microenvironment to inhibit CP fibrosis, identifying the CCL2/CCR2 axis as a key mechanism. Clinical samples revealed increased infiltration of CD11c+MHCII+CD68+ macrophages with reduced Lkb1 expression in fibrotic areas of CP patients. Lkb1 in CD11c+ cells inhibits CP fibrosis. Mechanistically, Lkb1 deficiency in CD11c+ cells enhances CCL2 secretion by CD11c+ macrophages via OSM-STAT3 activation. Concurrently, OSM signaling facilitates the interaction between CD11c+ macrophages and PSCs, promoting CCL2 secretion by PSCs. Pharmacological targeting of CCL2 using a CCL2/CCR2 inhibitor significantly attenuates fibrosis, reverses the infiltration of CD11c+CD206+ macrophage, and mitigates the exacerbated fibrosis induced by Lkb1 deficiency.
Conclusion:
This study identifies the CCL2-CCR2 axis as a key driver of fibrosis in CP mediated by Lkb1-deficient CD11c+ macrophages, offering a strong rationale for targeted therapy.
Chronic pancreatitis (CP) is a progressive fibrotic disease and the treatment landscape remains highly unsatisfactory. This study aims to elucidate the role of Lkb1 in CD11c+ macrophages within the immune microenvironment and fibrosis of CP.
Design:
The expression of Lkb1 in CD11c+ cells was assessed in pancreatic tissues from CP patients. Additionally, CD11cCreLkb1f/f and Lkb1f/f mice were utilized to establish a cerulein-induced CP model. Single-cell RNA sequencing, flow cytometry, and immunofluorescence revealed changes in the pancreatic immune microenvironment.
Results:
This study explores the role of Lkb1 in regulating the immune microenvironment to inhibit CP fibrosis, identifying the CCL2/CCR2 axis as a key mechanism. Clinical samples revealed increased infiltration of CD11c+MHCII+CD68+ macrophages with reduced Lkb1 expression in fibrotic areas of CP patients. Lkb1 in CD11c+ cells inhibits CP fibrosis. Mechanistically, Lkb1 deficiency in CD11c+ cells enhances CCL2 secretion by CD11c+ macrophages via OSM-STAT3 activation. Concurrently, OSM signaling facilitates the interaction between CD11c+ macrophages and PSCs, promoting CCL2 secretion by PSCs. Pharmacological targeting of CCL2 using a CCL2/CCR2 inhibitor significantly attenuates fibrosis, reverses the infiltration of CD11c+CD206+ macrophage, and mitigates the exacerbated fibrosis induced by Lkb1 deficiency.
Conclusion:
This study identifies the CCL2-CCR2 axis as a key driver of fibrosis in CP mediated by Lkb1-deficient CD11c+ macrophages, offering a strong rationale for targeted therapy.
- Index Term 1: Liver kinase B1
- Index Term 2: fibrosis