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Investigation of Macrophage Polarization Using Bone Marrow Derived Macrophages
Published on: June 23, 2013
Adenosine A2A receptor activation regulates the M1 macrophages activation to initiate innate and adaptive immunity in
Yan Lu1, Wu Zhu1, Guan Xiong Zhang1
1Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China; Hunan Key Laboratory of Skin Cancer and Psoriasis, Xiangya Hospital, Central South University, Changsha, China.
Abstract:
Psoriasis is a common inflammatory systemic disease characterized by pro-inflammatory macrophages activation (M1 macrophage) infiltrated in the dermal layer. How M1 macrophage contributes to psoriasis remains unknown. In this study, we found that adenosine A2A receptor (A2AR) agonist CGS 21680 HCl alleviated the imiquimod (IMQ) and mouse IL-23 Protein (rmIL-23)-induced psoriasis inflammation through reducing infiltration of M1. Conversely, Adora2a deletion in mice exacerbated psoriasis-like phenotype. Mechanistically, A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway to reduce the secretion of CXCL10/11 and inhibit Th1/17 differentiation. Notably, the KRT16 expression was first found in M1 macrophage in our study, not only in keratinocytes (KCs). CXCL10/11 are first identified as primarily derived from macrophages and dendritic cells (DCs) rather than KCs in psoriasis using single cell RNA sequencing (scRNA-Seq). In total, the study emphasizes the importance of M1 as an innate immune cell in pathogenesis of psoriasis.
Insights
Adenosine A2A receptor (A2AR) activation alleviates psoriasis by reducing M1 macrophage infiltration and activation. This study highlights M1 macrophages as key innate immune cells in psoriasis pathogenesis.
Area of Science:
- Immunology
- Dermatology
- Molecular Biology
Background:
- Psoriasis is a systemic inflammatory disease involving M1 macrophage infiltration.
- The precise role of M1 macrophages in psoriasis pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the role of adenosine A2A receptor (A2AR) in M1 macrophage-mediated psoriasis.
- To elucidate the molecular mechanisms by which A2AR influences psoriasis development.
Main Methods:
- Utilized imiquimod (IMQ) and recombinant mouse IL-23 (rmIL-23) induced psoriasis models in mice.
- Employed Adora2a gene deletion and A2AR agonist (CGS 21680 HCl) treatment.
- Applied single-cell RNA sequencing (scRNA-Seq) for cellular analysis.
Main Results:
- A2AR activation alleviated IMQ- and rmIL-23-induced psoriasis by reducing M1 macrophage infiltration.
- Adora2a deletion exacerbated psoriasis-like phenotypes.
- A2AR activation inhibited M1 macrophage activation via the NF-κB-KRT16 pathway, reducing CXCL10/11 secretion and Th1/17 differentiation.
- KRT16 was identified in M1 macrophages, and CXCL10/11 were found to originate primarily from macrophages and dendritic cells (DCs) in psoriasis.
Conclusions:
- A2AR signaling plays a protective role in psoriasis by modulating M1 macrophage activity.
- M1 macrophages are critical innate immune cells in the pathogenesis of psoriasis.
- Targeting A2AR may offer a therapeutic strategy for psoriasis.
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