Department of Respiratory Medicine and Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
Front Immunol. 2019 Mar 21;10:544. doi: 10.3389/fimmu.2019.00544. eCollection 2019.
Receptors recognizing the Fc-part of immunoglobulins (FcR) are important in the engagement of phagocytes with opsonized micro-organisms, but they also play a major role in the pathogenesis of chronic inflammatory diseases. Different FcRs are specifically recognizing and binding the different classes of immunoglobulins, transmitting different signals into the cell. The function of IgG (FcγR's) and IgA (FcαR) recognizing receptors is controlled by cellular signals evoked by activation of heterologous receptors in a process generally referred to as inside-out control. This concept is clearly described for the regulation of integrin receptors. Inside-out control can be achieved at different levels by modulation of: (i) receptor affinity, (ii) receptor avidity/valency, (iii) interaction with signaling chains, (iv) interaction with other receptors and (v) localization in functionally different membrane domains. The inside-out control of FcRs is an interesting target for novel therapy by therapeutical antibodies as it can potentiate or decrease the functionality of the response to the antibodies depending on the mechanisms of the diseases they are applied for.
识别免疫球蛋白 Fc 部分的受体（FcR）在吞噬细胞与调理微生物的结合中很重要，但它们在慢性炎症性疾病的发病机制中也起着主要作用。不同的 FcR 特异性识别和结合不同类别的免疫球蛋白，向细胞内传递不同的信号。识别受体 IgG（FcγR）和 IgA（FcαR）的功能受细胞信号的控制，这些信号是由异源受体的激活引发的，这个过程通常被称为内向外控制。这个概念在整合素受体的调节中被清楚地描述。内向外控制可以通过调节以下几个方面来实现：（i）受体亲和力，（ii）受体亲合力/价数，（iii）与信号链的相互作用，（iv）与其他受体的相互作用，以及（v）在功能不同的膜域中的定位。FcR 的内向外控制是治疗性抗体的一个有趣的治疗靶点，因为它可以根据应用于疾病的机制增强或降低对抗体的反应功能。
