白三烯D4和白介素13对人肺成纤维细胞白三烯受体1 mRNA表达及嗜酸粒细胞趋化因子产生的影响

探讨白三烯D4(LTD4)和白介素13(IL-13)对人肺成纤维细胞白三烯受体(CysLT1R)表达和eotaxin产生的影响。采用培养人肺成纤维细胞株(MRC-5),以不同浓度的IL-13进行刺激,用实时定量RT-PCR法测定CysLT1R mRNA表达的变化。再以不同浓度的LTD4和IL-13刺激,用ELISA法测定上清液中eotaxin的浓度,并观察Montelukast对eotaxin的产生是否有抑制作用。结果显示,培养的人肺成纤维细胞上存在着CysLT1R mRNA的低表达,以10 ng/ml IL-13刺激时,随着刺激时间延长,CysLT1R mRNA表达逐渐增高,48 h达高峰,较未刺激时表达增加(18.56±7.41)倍(P<0.01)。当以10 ng/ml和100 ng/ml的IL-13浓度刺激48 h时,较未刺激细胞CysLT1R mRNA表达分别增加(17.33±3.81)倍和(20.11±5.05)倍(P<0.01)。IL-13也能促进成纤维细胞产生eotaxin,以10 ng/ml和100 ng/ml的IL-13刺激成纤维细胞时,eotaxin浓度分别为(155.43±15.95)pg/ml和(221.31±17.23)pg/ml,较未刺激细胞(31.67±3.49)pg/ml明显增加(P<0.01)。单独给予LTD4刺激时,eotaxin浓度则无明显变化。但是以1×10-7mol/L和1×10-6mol/L浓度的LTD4分别联合10 ng/ml的IL-13共同刺激时,产生eotaxin的浓度分别为(204.4±25.4)pg/m和(255.1±38.3)pg/ml;较仅给予10 ng/ml的IL-13刺激时(155.4±16.0)pg/ml明显增加(P<0.01)。在LTD4+IL-13刺激组中,加入Mointelukast后eotaxin浓度为(148.3±15.7)pg/ml,较不加Montelukast(204.4±25.4)pg/ml明显降低(P<0.01)。人肺纤维细胞存在着CysLT1R mRNA的低表达,IL-13能够上调其表达,呈现时间与浓度依赖性。IL-13和LTD4对人肺成纤维细胞分泌的eoitaxin具有协同刺激作用,这可能与IL-13上调成纤维细胞CysLT1R mRNA表达有关,而Montelukast对这种刺激具有拮抗作用。     

IL-1R8: A molecular brake of anti-tumor and anti-viral activity of NK cells and ILC

Interleukin-1 receptor family members (ILRs) and Toll-Like Receptors (TLRs) play pivotal role in immunity and inflammation and are expressed by most cell types including cells of both the innate and adaptive immune system. In this context, IL-1 superfamily members are also important players in regulating function and differentiation of adaptive and innate lymphoid cells. This system is tightly regulated in order to avoid uncontrolled activation, which may lead to detrimental inflammation contributing to autoimmune or allergic responses. IL-1R8 (also known as TIR8 or SIGIRR) is a member of the IL-1R family that acts as a negative regulator dampening ILR and TLR signaling and as a co-receptor for human IL-37. Human and mouse NK cells, that are key players in immune surveillance of tumors and infections, express high level of IL-1R8. In this review, we will summarize our current understanding on the structure, expression and function of IL-1R8 and we will also discuss the emerging role of IL-1R8 as an important checkpoint regulating NK cells function in pathological conditions including cancer and viral infections.     

ILC2: at home in the thymus

The relevance of innate lymphoid cells (ILC) for anti‐infectious immunity remains a matter of constant debate. At the same time, evidence for additional, non‐immune related functions of ILC is steadily increasing. In the thymus, non‐immune functions of ILC were shown for group 3 ILC (ILC3), which regulate differentiation and proliferation of thymic epithelial cells. In this issue of the European Journal of Immunology, Withers and colleagues [Eur. J. Immunol. 2018. 48: 1481–1491] now show that ILC2, a subset of ILCs specialized in tissue protection and regeneration, are the major ILC subset in the adult thymus, heavily outnumbering ILC3. These findings raise novel questions on the function of thymic ILC, and warrant re‐evaluation of the importance of ILC2 and their cytokines during thymic function and repair.     

ILC2 memory: Recollection of previous activation

Immunological memory, traditionally thought to belong to T and B cells, has now been extended to innate lymphocytes, including NK cells and ILC2s, myeloid cells such as macrophages, also termed “trained immunity” and more recently to epithelial stem cells. In this review, we discuss the mechanisms underlying memory generation on ILC2s and speculate about their potential role in human allergic diseases, such as asthma. Moreover, we examine the relevance of the spontaneous ILC2 activation in the lung during the neonatal period in order to efficiently respond to stimuli later in life. These “training” of neonatal ILC2s may have an impact on the generation of memory ILC2s in the adulthood.