Miyake Kensuke, Shiozawa Nozomu, Nagao Toshihisa, Yoshikawa Soichiro, Yamanishi Yoshinori, Karasuyama Hajime
Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan.
Department of Immune Regulation, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo 113-8510, Japan
Proc Natl Acad Sci U S A. 2017 Jan 31;114(5):1111-1116. doi: 10.1073/pnas.1615973114. Epub 2017 Jan 17.
Th2 immunity plays important roles in both protective and allergic responses. Nevertheless, the nature of antigen-presenting cells responsible for Th2 cell differentiation remains ill-defined compared with the nature of the cells responsible for Th1 and Th17 cell differentiation. Basophils have attracted attention as a producer of Th2-inducing cytokine IL-4, whereas their MHC class II (MHC-II) expression and function as antigen-presenting cells are matters of considerable controversy. Here we revisited the MHC-II expression on basophils and explored its functional relevance in Th2 cell differentiation. Basophils generated in vitro from bone marrow cells in culture with IL-3 plus GM-CSF displayed MHC-II on the cell surface, whereas those generated in culture with IL-3 alone did not. Of note, these MHC-II-expressing basophils showed little or no transcription of the corresponding MHC-II gene. The GM-CSF addition to culture expanded dendritic cells (DCs) other than basophils. Coculture of basophils and DCs revealed that basophils acquired peptide-MHC-II complexes from DCs via cell contact-dependent trogocytosis. The acquired complexes, together with CD86, enabled basophils to stimulate peptide-specific T cells, leading to their proliferation and IL-4 production, indicating that basophils can function as antigen-presenting cells for Th2 cell differentiation. Transfer of MHC-II from DCs to basophils was also detected in draining lymph nodes of mice with atopic dermatitis-like skin inflammation. Thus, the present study defined the mechanism by which basophils display MHC-II on the cell surface and appears to reconcile some discrepancies observed in previous studies.
Th2免疫在保护性反应和过敏性反应中均发挥着重要作用。然而，与负责Th1和Th17细胞分化的细胞性质相比，负责Th2细胞分化的抗原呈递细胞的性质仍不明确。嗜碱性粒细胞作为Th2诱导细胞因子IL-4的产生者已受到关注，而其MHC II类（MHC-II）表达及作为抗原呈递细胞的功能存在相当大的争议。在此，我们重新审视了嗜碱性粒细胞上的MHC-II表达，并探讨了其在Th2细胞分化中的功能相关性。在含有IL-3加GM-CSF的培养基中由骨髓细胞体外生成的嗜碱性粒细胞在细胞表面显示MHC-II，而仅在含有IL-3的培养基中生成的嗜碱性粒细胞则不显示。值得注意的是，这些表达MHC-II的嗜碱性粒细胞几乎没有或没有相应MHC-II基因的转录。向培养基中添加GM-CSF可使除嗜碱性粒细胞外的树突状细胞（DC）扩增。嗜碱性粒细胞与DC的共培养显示，嗜碱性粒细胞通过细胞接触依赖性胞啃作用从DC获得肽-MHC-II复合物。获得的复合物与CD86一起，使嗜碱性粒细胞能够刺激肽特异性T细胞，导致其增殖和IL-4产生，表明嗜碱性粒细胞可作为Th2细胞分化的抗原呈递细胞发挥作用。在患有特应性皮炎样皮肤炎症的小鼠引流淋巴结中也检测到了MHC-II从DC转移至嗜碱性粒细胞。因此，本研究确定了嗜碱性粒细胞在细胞表面显示MHC-II的机制，并且似乎调和了先前研究中观察到的一些差异。
