Rivera Juan, Fierro Nora A, Olivera Ana, Suzuki Ryo
Laboratory of Immune Cell Signaling, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Adv Immunol. 2008;98:85-120. doi: 10.1016/S0065-2776(08)00403-3.
Mast cells are innate immune cells that function as regulatory or effector cells and serve to amplify adaptive immunity. In adaptive immunity these cells function primarily through cell surface Fc receptors that bind immunoglobulin antibodies. The dysregulation of their adaptive role makes them central players in allergy and asthma. Upon encountering an allergen (antigen), which is recognized by immunoglobulin E (IgE) antibodies bound to the high affinity IgE receptor (FcepsilonRI) expressed on their cell surface, mast cells secrete both preformed and newly synthesized mediators of the allergic response. Blocking of these responses is an objective in therapeutic intervention of allergic diseases. Thus, understanding the mechanisms by which antigens elicit mast cell activation (via FcepsilonRI) holds promise toward identifying therapeutic targets. Here we review the most recent advances in understanding antigen-dependent mast cell activation. Specifically, we focus on the requirements for FcepsilonRI activation, the regulation of calcium responses, co-stimulatory signals in FcepsilonRI-mediated mast cell activation and function, and how genetics influences mast cell signaling and responses. These recent discoveries open new avenues of investigation with therapeutic potential.
肥大细胞是先天性免疫细胞，作为调节细胞或效应细胞发挥作用，并有助于增强适应性免疫。在适应性免疫中，这些细胞主要通过与免疫球蛋白抗体结合的细胞表面Fc受体发挥作用。其适应性作用的失调使其成为过敏和哮喘的关键因素。当遇到过敏原（抗原）时，该过敏原被结合在其细胞表面表达的高亲和力IgE受体（FcepsilonRI）上的免疫球蛋白E（IgE）抗体识别，肥大细胞会分泌预先形成的和新合成的过敏反应介质。阻断这些反应是过敏性疾病治疗干预的一个目标。因此，了解抗原引发肥大细胞活化（通过FcepsilonRI）的机制有望确定治疗靶点。在此，我们综述了在理解抗原依赖性肥大细胞活化方面的最新进展。具体而言，我们关注FcepsilonRI活化的要求、钙反应的调节、FcepsilonRI介导的肥大细胞活化和功能中的共刺激信号，以及遗传学如何影响肥大细胞信号传导和反应。这些最新发现开辟了具有治疗潜力的新研究途径。
