
IgE 與 FcεRI 的結合會導致 FcεRI 從二聚體解離成單體，進而引發下游信號傳遞和過敏反應。


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Molecular mechanism of IgE-mediated FcεRI activation - Nature

ige-介導的-fcεri-活化分子機制研究


IgE 介導的 FcεRI 活化分子機制研究


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인간 비만 세포에서 IgE 결합 전 FcεRI는 이량체 형태로 존재하며, IgE 결합 시 단량체로 분리되어 알레르기 반응을 활성화한다.


ige-매개-fcεri-활성화의-분자-메커니즘-이량체에서-단량체로의-전환을-통한-알레르기-반응-활성화


IgE 매개 FcεRI 활성화의 분자 메커니즘: 이량체에서 단량체로의 전환을 통한 알레르기 반응 활성화



IgE 結合前の FcεRI は細胞膜上で二量体を形成しており、IgE 結合により二量体が解離して単量体となることで、アレルギー反応を引き起こすシグナル伝達経路が活性化される。


ige-を介した-fcεri-活性化の分子メカニズム-二量体から単量体への移行が鍵となる


IgE を介した FcεRI 活性化の分子メカニズム：二量体から単量体への移行が鍵となる



The high-affinity IgE receptor (FcεRI) exists as a dimer on mast cells, and IgE binding induces its dissociation into monomers, triggering downstream signaling and allergic responses.


the-dimer-to-monomer-transition-of-fcεri-activates-ige-mediated-allergic-responses


The Dimer-to-Monomer Transition of FcεRI Activates IgE-Mediated Allergic Responses



The N-glycan at position 162 of the FcγRIIIa receptor plays a crucial role in regulating antibody binding affinity and the potency of natural killer (NK) cell antibody-dependent cell-mediated cytotoxicity (ADCC).


Both endogenous antibodies and a subset of antibody therapeutics engage Fc gamma receptor (FcγR)IIIa / CD16a to stimulate a protective immune response. Increasing the FcγRIIIa/IgG1 interaction improves the immune response and thus represents a strategy to improve therapeutic efficacy. FcγRIIIa is a heavily glycosylated receptor and glycan composition affects antibody-binding affinity. Though our laboratory previously demonstrated that natural killer (NK) cell N-glycan composition affected the potency of one key protective mechanism, antibody-dependent cell-mediated cytotoxicity (ADCC), it was unclear if this effect was due to FcγRIIIa glycosylation. Furthermore, the structural mechanism linking glycan composition to affinity and cellular activation remained undescribed. To define the role of individual amino acid and N-glycan residues we measured affinity using multiple FcγRIIIa glycoforms. We observed stepwise affinity increases with each glycan truncation step with the most severely truncated glycoform displaying the highest affinity. Removing the N162 glycan demonstrated its predominant role in regulating antibody-binding affinity, in contrast to four other FcγRIIIa N-glycans. We next evaluated the impact of the N162 glycan on NK cell ADCC. NK cells expressing the FcγRIIIa V158 allotype exhibited increased ADCC following kifunensine treatment to limit N-glycan processing. Notably, an increase was not observed with cells expressing the FcγRIIIa V158 S164A variant that lacks N162 glycosylation, indicating the N162 glycan is required for increased NK cell ADCC. To gain structural insight into the mechanisms of N162 regulation, we applied a novel protein isotope labeling approach in combination with solution NMR spectroscopy. FG loop residues proximal to the N162 glycosylation site showed large chemical shift perturbations following glycan truncation. These data support a model for the regulation of FcγRIIIa affinity and NK cell ADCC whereby composition of the N162 glycan stabilizes the FG loop and thus the antibody-binding site.

### Competing Interest Statement

The authors have declared no competing interest.

One N-glycan regulates natural killer cell antibody-dependent cell-mediated cytotoxicity and modulates Fc γ receptor IIIa / CD16a structure

the-n162-glycan-on-fcγriiia-cd16a-regulates-antibody-binding-affinity-and-natural-killer-cell-adcc


The N162 Glycan on FcγRIIIa/CD16a Regulates Antibody Binding Affinity and Natural Killer Cell ADCC



神經肽 CGRP 通過與 T 細胞上的受體 RAMP3 結合，促進 TH1 細胞分化和抗病毒免疫反應。


RAMP3, a component of the receptor for the neuropeptide CGRP, has a cell-intrinsic role in T helper type 1 cell fate determination.

Neuropeptide signalling orchestrates T cell differentiation - Nature

神經肽訊號調控-t-細胞分化-cgrp-ramp3-軸促進-th1-細胞免疫反應


神經肽訊號調控 T 細胞分化：CGRP-RAMP3 軸促進 TH1 細胞免疫反應



神経ペプチドCGRPは、急性ウイルス感染時にニューロンから産生され、T細胞上の受容体RAMP3に作用することでTH1細胞への分化を促進し、効果的な抗ウイルス免疫応答を誘導する。


神経ペプチドシグナル伝達はt細胞の分化を制御する


神経ペプチドシグナル伝達はT細胞の分化を制御する



Neuronal CGRP, signaling through the RAMP3 receptor on T cells, plays a crucial role in promoting TH1 cell differentiation and enhancing antiviral immunity during acute viral infection.


neuropeptide-cgrp-signaling-via-ramp3-regulates-t-helper-cell-differentiation-and-antiviral-response


Neuropeptide CGRP Signaling via RAMP3 Regulates T Helper Cell Differentiation and Antiviral Response



PD-1的共抑制信號不僅降低了效應T細胞活性的強度，而且還改變了CD4+ T細胞的功能分化，強烈抑制Th2細胞的產生，並可能成為治療過敏性疾病的潛在靶點。


Programmed Cell Death Protein-1 (PD-1) represents endogenous mechanisms of negative immunoregulation. While the modulation of effector functions has been the major focus of PD-1 research, quick PD-1 upregulation in naïve T cells starting 1 h after priming raised a possibility that PD-1 also affects the development of effector T cells. The role of PD-1 in functional differentiation into Th1 and Th2 has been unclear. In murine naïve CD4+ T cell activation, we found that PD-1 stimulation during the early stage of T cell activation strongly impaired Th2 cell development, while Th1 cell induction was relatively resistant to this immunosuppressive signaling. The steep decline in Th2 cell induction suggested the significance of PD-1 in allergic inflammation. Treatment with anti-human PD-1 agonist antibody inhibited allergic inflammation in human PD-1-knock-in mice as shown by the reduction of Th2 cells, IgE levels and eosinophilic infiltration. This study shows that PD-1 regulates not only the intensity but also the quality of immune response by deviating Th differentiation. PD-1 stimulators are projected to be valuable in suppressing various forms of inflammatory activities, but the efficacy against Th2-dominant immune response may be particularly high.

### Competing Interest Statement

M.T., K.S., Y.T., T.H. and A.O. are inventors on patent applications (WO2021/241523A1, WO2022/239820) submitted by Foundation for Biomedical Research and Innovation at Kobe, National Institutes of Biomedical Innovation, Health and Nutrition, and Meiji Seika Pharma Co. Ltd. that cover anti-human PD-1 agonist antibodies and their therapeutic application. K.S. and Y.T. are employees of Meiji Seika Pharma Co. Ltd. The remaining authors declare no competing interests.

PD-1 negatively regulates helper T cell differentiation into Th2

pd-1通過抑制th2細胞分化負向調節輔助性t細胞分化


PD-1通過抑制Th2細胞分化負向調節輔助性T細胞分化



免疫チェックポイント分子であるPD-1は、T細胞の活性化を抑制するだけでなく、Th2細胞への分化を強く抑制することでアレルギー性炎症を制御する可能性を持つ。


pd-1はth2細胞へのヘルパーt細胞分化を負に制御する


PD-1はTh2細胞へのヘルパーT細胞分化を負に制御する
