A role for FcγRIIB in the development of murine bleomycin-induced fibrosis
| Autor: | Akito Komuro, Kazuhiko Takehara, Kyosuke Oishi, Yuka Ikawa, Shintaro Maeda, Kaori Sawada, Yasuhito Hamaguchi, Takashi Matsushita, Kie Mizumaki |
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| Rok vydání: | 2021 |
| Předmět: |
Chemokine
Adoptive cell transfer medicine.medical_treatment CCL3 Dermatology CD8-Positive T-Lymphocytes Bleomycin Biochemistry Mice chemistry.chemical_compound Fibrosis medicine Animals Molecular Biology Skin Scleroderma Systemic integumentary system biology business.industry medicine.disease Disease Models Animal CXCL2 Cytokine chemistry Immunology biology.protein business CD8 |
| Zdroj: | Journal of Dermatological Science. 104:201-209 |
| ISSN: | 0923-1811 |
| DOI: | 10.1016/j.jdermsci.2021.11.002 |
| Popis: | Background Systemic sclerosis (SSc) is a systemic autoimmune disease characterized by excessive fibrosis. FcγRIIB is a low-affinity receptor for the Fc fragment of IgG. FcγRIIB is expressed on the surface of various leukocyte subsets and signals negative feedback pathways to down-regulate B-cell antigen receptor signaling. Objective The aim of the present study was to investigate the role of FcγRIIB in the development of a murine bleomycin-induced scleroderma model. Methods The experimental fibrosis model was generated by the subcutaneous injection of bleomycin into wild-type (WT) and FcγRIIB-deficient (FcγRIIB-/-) mice. We histologically assessed skin and lung fibrosis as well as inflammatory cell infiltration. Cytokine and chemokine expression levels were measured with RT-PCR. Results The severity of fibrosis in the skin and lung was significantly worse in FcγRIIB-/- mice than in WT mice. In the skin of bleomycin-treated mice, the numbers of CD8+ T cells, F4/80+ macrophages, MPO+ neutrophils, NK1.1+NK cells, and B220+ B cells were significantly higher in FcγRIIB-/- mice than in WT mice. The expression of TNF-α and IL-1β was significantly higher in FcγRIIB-/- mice than in WT mice as was the expression of ICAM-1, CXCL2, and CCL3 in the affected skin. An adoptive transfer of splenic leukocytes from FcγRIIB-/- mice into WT mice showed exacerbated skin and lung fibrosis compared to WT mice without an adoptive transfer. Conclusion These results indicate that FcγRIIB plays an inhibitory role in skin and lung fibrosis. Moreover, modulating FcγRIIB signaling has potential as a therapeutic approach for SSc. |
| Databáze: | OpenAIRE |
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