Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Pharmacology and Experimental Therapeutics Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
J Leukoc Biol. 2019 Oct;106(4):957-966. doi: 10.1002/JLB.3A1018-389R. Epub 2019 May 20.
CD300a is an inhibitory immunoreceptor expressed in lymphoid and myeloid cells. This study evaluates whether CD300a plays a role in the control of joint inflammation in a model of Ag-induced arthritis (AIA) in mice. CD300a was found to be expressed mostly on neutrophils and its expression was enhanced on neutrophils that migrated to the inflamed synovial cavity. Joint inflammation, as characterized by neutrophil accumulation, was significantly greater in CD300a KO (CD300a ) mice subjected to AIA, as compared to WT mice. This was associated with joint dysfunction, as measured by lower mechanical nociception threshold. There was greater production of the chemokine CXCL1 and the cytokine IL-6 in joints of CD300a mice. In vitro, Mϕs from CD300a mice released higher concentrations of CXCL1 and IL-6 in response to LPS. Splenocytes from immunized CD300a mice produced increased levels of IFN-γ and IL-17 and lower levels of IL-10 when challenged with Ag than cells from WT mice. Neutrophils lacking the CD300a gene had greater chemotactic activity in response to fMLP, CXCL1, and LTB4 than WT neutrophils. In conclusion, these results reveal that the absence of CD300a promotes exacerbation of inflammation in a model of Ag-induced arthritis, suggesting that CD300a is an important receptor for negatively controlling the inflammatory response in this model. Mechanistically, CD300a seems to regulate the activity of various immune cells types involved in the process, including neutrophils, Mϕs, and lymphocytes.
CD300a 是一种在淋巴样细胞和髓样细胞中表达的抑制性免疫受体。本研究评估了 CD300a 是否在 Ag 诱导的关节炎（AIA）小鼠模型中控制关节炎症中发挥作用。研究发现，CD300a 主要表达于中性粒细胞，其在迁移到炎症滑膜腔的中性粒细胞上的表达增强。与 WT 小鼠相比，在 AIA 中，CD300a 敲除（CD300a KO）小鼠的关节炎症（以中性粒细胞积累为特征）明显更严重。这与关节功能障碍有关，表现为机械性痛觉过敏阈值降低。CD300a 小鼠关节中趋化因子 CXCL1 和细胞因子 IL-6 的产生增加。体外，CD300a 小鼠的 Mϕ 对 LPS 的反应释放更高浓度的 CXCL1 和 IL-6。与 WT 小鼠相比，用 Ag 刺激的免疫 CD300a 小鼠的脾细胞产生更高水平的 IFN-γ和 IL-17，而产生的 IL-10 水平更低。缺乏 CD300a 基因的中性粒细胞对 fMLP、CXCL1 和 LTB4 的趋化活性高于 WT 中性粒细胞。总之，这些结果表明 CD300a 的缺失促进了 Ag 诱导关节炎模型中炎症的加重，表明 CD300a 是该模型中负调控炎症反应的重要受体。从机制上讲，CD300a 似乎调节参与该过程的各种免疫细胞类型的活性，包括中性粒细胞、Mϕ 和淋巴细胞。
