Project Details
Projekt
Unravelling the role of IL-23 secretion by efferocytic macrophages in maintaining and reestablishing intestinal homeostasis
Applicant
Lidia Bosurgi, Ph.D.
Subject Area
Cell Biology
Gastroenterology
Immunology
Gastroenterology
Immunology
Term
since 2025
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 533863915
Efferocytosis is essential for maintaining tissue homeostasis and facilitating recovery following damage. Typically, efferocytosis is considered an immunosilent process that minimally affects macrophage cytokine secretion. However, our preliminary data reveal that macrophages release IL-23 upon apoptotic cell uptake. IL-23, a heterodimeric pro-inflammatory cytokine, is known to be secreted by macrophages in response to commensal bacteria and is highly expressed in the inflamed mucosa of patients with inflammatory bowel disease (IBD), where it drives the differentiation of pathogenic Th17 cells. Consequently, blocking IL-23 is a current therapeutic option for IBD patients. However, whether IL-23 is secreted by colon efferocytic macrophages and its impact on the intestinal environment is completely unknown. We hypothesize that efferocytosis prompts macrophages to secrete the proinflammatory cytokine IL-23, and this in turn regulates intestinal structural integrity during physiological and reparative regeneration. In particular, we postulate that IL-23 targets colon fibroblasts in homeostasis and during the progression of chronic colitis, tipping the balance between tissue regeneration and fibrosis development. Based on this, we aim to first decipher the cellular triggers and molecular signature of IL-23 secretion by efferocytic macrophages. Particular attention will be given to differences in the magnitude of IL-23 response upon uptake of apoptotic cells with distinct cellular identities using our established in vitro models. Finally, we will investigate the impact of efferocytosis-derived IL-23 on fibroblast activation and fibrosis development during colon homeostasis and in a murine model of chronic colitis. Collectively, the data generated could reveal a previously unknown source of IL-23 in the intestine and elucidate a new role for phagocytic macrophages in controlling the shift from tissue remodelling to fibrosis development during IBD progression.
DFG Programme
Research Units
