C-Reactive Protein Suppresses the Th17 Response Indirectly by Attenuating the Antigen Presentation Ability of Monocyte Derived Dendritic Cells in Experimental Autoimmune Encephalomyelitis
| Autor: | Yi Zheng, Ke Wang, Wei Li, Min-Jie Gong, Zhi-Yuan Shen, Feng Wu, Maggie K. Pecsok, Lin Zhang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
experimental autoimmune encephalomyelitis Gene Expression Lymphocyte Activation Monocytes Mice 0302 clinical medicine T-Lymphocyte Subsets FcγR2B Immunology and Allergy Original Research Antigen Presentation Experimental autoimmune encephalomyelitis Cell Differentiation monocyte derived DC Cytokines Signal Transduction lcsh:Immunologic diseases. Allergy Encephalomyelitis Autoimmune Experimental Multiple Sclerosis Th17 response Immunology Antigen presentation Immunophenotyping C-reactive protein Immunomodulation 03 medical and health sciences Immune system Antigen Downregulation and upregulation In vivo medicine Animals Antigen-presenting cell Autoimmune disease business.industry Receptors IgG Histocompatibility Antigens Class II Dendritic Cells medicine.disease Disease Models Animal 030104 developmental biology Th17 Cells B7-2 Antigen lcsh:RC581-607 business Biomarkers Spleen 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 12 (2021) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2021.589200 |
| Popis: | Experimental autoimmune encephalomyelitis (EAE) is a classical murine model for Multiple Sclerosis (MS), a human autoimmune disease characterized by Th1 and Th17 responses. Numerous studies have reported that C-reactive protein (CRP) mitigates EAE severity, but studies on the relevant pathologic mechanisms are insufficient. Our previous study found that CRP suppresses Th1 response directly by receptor binding on naïve T cells; however, we did not observe the effect on Th17 response at that time; thus it remains unclear whether CRP could regulate Th17 response. In this study, we verified the downregulation of Th17 response by a single-dose CRP injection in MOG-immunized EAE mice in vivo while the direct and indirect effects of CRP on Th17 response were differentiated by comparing its actions on isolated CD4+ T cells and splenocytes in vitro, respectively. Moreover, the immune cell composition was examined in the blood and CNS (Central Nervous System), and a blood (monocytes) to CNS (dendritic cells) infiltration pathway is established in the course of EAE development. The infiltrated monocyte derived DCs (moDCs) were proved to be the only candidate antigen presenting cells to execute CRP’s function. Conversely, the decrease of Th17 responses caused by CRP disappeared in the above in vivo and in vitro studies with FcγR2B−/− mice, indicating that FcγR2B expressed on moDCs mediates CRP function. Furthermore, peripheral blood monocytes were isolated and induced to establish moDCs, which were used to demonstrate that the antigen presenting ability of moDCs was attenuated by CRP through FcγR2B, and then NF-κB and ERK signaling pathways were manifested to be involved in this regulation. Ultimately, we perfected and enriched the mechanism studies of CRP in EAE remission, so we are more convinced that CRP plays a key role in protecting against EAE development, which may be a potential therapeutic target for the treatment of MS in human. |
| Databáze: | OpenAIRE |
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