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Depletion and Reconstitution of Macrophages in Mice
Published on: August 1, 2012
CD169+ Skin Macrophages Function as a Specialized Subpopulation in Promoting Psoriasis-like Skin Disease in Mice
Mengyao Li1, Wenjing Yu1, Zhiduo Liu1
1Department of Immunology and Microbiology, Shanghai Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Abstract:
Skin macrophages are critical to maintain and restore skin homeostasis. They serve as major producers of cytokines and chemokines in the skin, participating in diverse biological processes such as wound healing and psoriasis. The heterogeneity and functional diversity of macrophage subpopulations endow them with multifaceted roles in psoriasis development. A distinct subpopulation of skin macrophages, characterized by high expression of CD169, has been reported to exist in both mouse and human skin. However, its role in psoriasis remains unknown. Here, we report that CD169+ macrophages exhibit increased abundance in imiquimod (IMQ) induced psoriasis-like skin lesions. Specific depletion of CD169+ macrophages in CD169-ditheria toxin receptor (CD169-DTR) mice inhibits IMQ-induced psoriasis, resulting in milder symptoms, diminished proinflammatory cytokine levels and reduced proportion of Th17 cells within the skin lesions. Furthermore, transcriptomic analysis uncovers enhanced activity in CD169+ macrophages when compared with CD169- macrophages, characterized by upregulated genes that are associated with cell activation and cell metabolism. Mechanistically, CD169+ macrophages isolated from IMQ-induced skin lesions produce more proinflammatory cytokines and exhibit enhanced ability to promote Th17 cell differentiation in vitro. Collectively, our findings highlight the crucial involvement of CD169+ macrophages in psoriasis development and offer novel insights into the heterogeneity of skin macrophages in the context of psoriasis.
Insights
CD169-positive macrophages are abundant in psoriasis lesions and promote disease development. Depleting these cells reduces psoriasis symptoms and inflammation, revealing their critical role in skin homeostasis.
Area of Science:
- Immunology
- Dermatology
- Cell Biology
Background:
- Skin macrophages are crucial for skin homeostasis, wound healing, and inflammatory conditions like psoriasis.
- Macrophage subpopulations exhibit diverse roles in disease pathogenesis.
- The specific function of CD169-positive (CD169+) skin macrophages in psoriasis is currently unknown.
Purpose of the Study:
- To investigate the role of CD169+ macrophages in the development of psoriasis.
- To determine the functional characteristics of CD169+ macrophages in skin inflammation.
Main Methods:
- Utilized imiquimod (IMQ)-induced mouse model for psoriasis-like skin lesions.
- Employed CD169-diphtheria toxin receptor (CD169-DTR) mice for specific depletion of CD169+ macrophages.
- Performed transcriptomic analysis to compare CD169+ and CD169- macrophages.
- Assessed Th17 cell differentiation in vitro.
Main Results:
- CD169+ macrophages were found in increased abundance in IMQ-induced psoriasis-like lesions.
- Depletion of CD169+ macrophages significantly inhibited IMQ-induced psoriasis, leading to milder symptoms.
- Reduced levels of proinflammatory cytokines and a lower proportion of Th17 cells were observed in depleted mice.
- Transcriptomic analysis revealed heightened cell activation and metabolic activity in CD169+ macrophages.
- Isolated CD169+ macrophages produced more proinflammatory cytokines and enhanced Th17 cell differentiation in vitro.
Conclusions:
- CD169+ macrophages play a critical role in the development and exacerbation of psoriasis.
- These macrophages exhibit distinct functional properties contributing to skin inflammation.
- Targeting CD169+ macrophages may represent a novel therapeutic strategy for psoriasis.
- Findings provide new insights into skin macrophage heterogeneity in psoriasis.
