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Jagged1 Instructs Macrophage Differentiation in Leprosy
Jon Kibbie1, Rosane M B Teles2, Zhiming Wang3
1Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, California, United States of America.
Plos Pathogens
|August 18, 2016
Summary
Endothelial cells instruct monocyte differentiation into macrophages. The IFN-γ-JAG1 axis, identified in leprosy, drives antimicrobial M1 macrophage development, crucial for host defense.
Area of Science:
- Immunology
- Cell Biology
- Infectious Diseases
Background:
- Monocyte differentiation into tissue macrophages (MΦ) is directed by the local microenvironment.
- Human leprosy exhibits distinct MΦ subtypes: M1 in self-limited disease and M2 in progressive disease.
Purpose of the Study:
- To elucidate mechanisms regulating macrophage differentiation.
- To investigate the role of endothelial cells (EC) and specific molecular pathways in MΦ polarization.
Main Methods:
- Utilized a heterotypic co-culture model of monocytes and endothelial cells.
- Performed biochemical screens and gene expression profiling.
- Analyzed Jagged1 (JAG1) expression and function in leprosy lesions and in vitro models.
Main Results:
- Unstimulated EC induced M2 MΦ differentiation.
- IFN-γ and small molecules activated EC to induce M1 MΦ differentiation.
- JAG1 was identified as a key regulator, with its expression correlating with M1 MΦ induction and leprosy form.
Conclusions:
- The IFN-γ-JAG1 axis plays a critical role in instructing monocyte to M1 MΦ differentiation.
- This pathway is implicated in the host defense response at disease sites, particularly in human leprosy.
- Targeting the IFN-γ-JAG1 axis may offer therapeutic strategies for infectious diseases.
