دورية أكاديمية
أعرض في EDS

The Inhibitory Receptor Siglec-8 Interacts With FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation.

التفاصيل البيبلوغرافية
العنوان: The Inhibitory Receptor Siglec-8 Interacts With FcεRI and Globally Inhibits Intracellular Signaling in Primary Mast Cells Upon Activation.
المؤلفون: Korver W; Allakos Inc., Redwood City, CA, United States., Wong A; Allakos Inc., Redwood City, CA, United States., Gebremeskel S; Allakos Inc., Redwood City, CA, United States., Negri GL; LM Biostat Consulting Inc., Victoria, BC, Canada., Schanin J; Allakos Inc., Redwood City, CA, United States., Chang K; Allakos Inc., Redwood City, CA, United States., Leung J; Allakos Inc., Redwood City, CA, United States., Benet Z; Allakos Inc., Redwood City, CA, United States., Luu T; Allakos Inc., Redwood City, CA, United States., Brock EC; Allakos Inc., Redwood City, CA, United States., Luehrsen K; Allakos Inc., Redwood City, CA, United States., Xu A; Allakos Inc., Redwood City, CA, United States., Youngblood BA; Allakos Inc., Redwood City, CA, United States.
المصدر: Frontiers in immunology [Front Immunol] 2022 Jan 28; Vol. 13, pp. 833728. Date of Electronic Publication: 2022 Jan 28 (Print Publication: 2022).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Lausanne : Frontiers Research Foundation]
مواضيع طبية MeSH: Antigens, CD/*metabolism , Antigens, Differentiation, B-Lymphocyte/*metabolism , Lectins/*metabolism , Mast Cells/*immunology , Receptors, IgE/*metabolism, Animals ; Cell Degranulation ; Humans ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/metabolism ; Proteomics ; Signal Transduction
مستخلص: Immunomodulation of mast cell (MC) activity is warranted in allergic and inflammatory diseases where MCs have a central role in pathogenesis. Targeting Siglec-8, an inhibitory receptor on MCs and eosinophils, has shown promising activity in preclinical and clinical studies. While the intracellular pathways that regulate Siglec-8 activity in eosinophils have been well studied, the signaling mechanisms that lead to MC inhibition have not been fully elucidated. Here, we evaluate the intracellular signaling pathways of Siglec-8-mediated inhibition in primary MCs using an anti-Siglec-8 monoclonal antibody (mAb). Phospho-proteomic profiling of FcεRI-activated MCs revealed Siglec-8 mAb-treatment globally inhibited proximal and downstream kinases, leading to attenuated MC activation and degranulation. In fact, Siglec-8 was found to directly interact with FcεRI signaling molecules. Siglec-8 inhibition was dependent on both cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) that interact with the SH2 containing protein phosphatase Shp-2 upon Siglec-8 phosphorylation. Taken together, these data support a model in which Siglec-8 regulates proximal FcεRI-induced phosphorylation events through phosphatase recruitment and interaction with FcεRIγ, resulting in global inhibition of MCs upon Siglec-8 mAb engagement.
Competing Interests: WK, AW, SG, JS, KC, JL, ZB, TL, EB, KL, AX and BY were employed by Allakos Inc. GN was employed by LM Biostat Consulting Inc. The authors declare that this study received funding from Allakos Inc. The funder had the following involvement with the study: data collection, analysis, interpretation, study design, and writing of this article.
(Copyright © 2022 Korver, Wong, Gebremeskel, Negri, Schanin, Chang, Leung, Benet, Luu, Brock, Luehrsen, Xu and Youngblood.)
References: Nat Rev Immunol. 2014 Oct;14(10):653-66. (PMID: 25234143)
J Allergy Clin Immunol. 2007 Mar;119(3):544-52; quiz 553-4. (PMID: 17336609)
Front Immunol. 2021 Oct 11;12:737988. (PMID: 34721399)
J Immunol. 2007 Nov 1;179(9):5864-76. (PMID: 17947660)
JCI Insight. 2019 Oct 3;4(19):. (PMID: 31465299)
Front Immunol. 2021 Mar 10;12:650331. (PMID: 33777047)
J Biol Chem. 2000 Jan 14;275(2):861-6. (PMID: 10625619)
Int Immunol. 2005 Jun;17(6):685-94. (PMID: 15944196)
Proc Natl Acad Sci U S A. 2013 Jul 23;110(30):12402-7. (PMID: 23836650)
Cell. 1998 Feb 20;92(4):441-50. (PMID: 9491886)
J Allergy Clin Immunol. 2008 Feb;121(2):499-505.e1. (PMID: 18036650)
J Exp Med. 2012 Jun 4;209(6):1201-17. (PMID: 22641383)
Commun Biol. 2020 Mar 17;3(1):128. (PMID: 32184441)
Blood. 2003 Jun 15;101(12):5014-20. (PMID: 12609831)
Int Arch Allergy Immunol. 2019;180(2):91-102. (PMID: 31401630)
Nucleic Acids Res. 2015 Jan;43(Database issue):D512-20. (PMID: 25514926)
J Immunol. 2021 May 15;206(10):2290-2300. (PMID: 33911007)
Annu Rev Immunol. 2020 Apr 26;38:365-395. (PMID: 31986070)
Allergy. 2012 Oct;67(10):1241-9. (PMID: 22845063)
J Allergy Clin Immunol. 2018 Jun;141(6):2196-2207. (PMID: 28888781)
J Allergy Clin Immunol. 2000 Jun;105(6 Pt 1):1093-100. (PMID: 10856141)
Proc Natl Acad Sci U S A. 2021 Aug 31;118(35):. (PMID: 34433665)
Front Immunol. 2014 Nov 14;5:569. (PMID: 25452755)
J Immunol. 2004 Dec 1;173(11):6841-9. (PMID: 15557178)
Clin Rev Allergy Immunol. 2020 Jun;58(3):377-387. (PMID: 32086776)
Mucosal Immunol. 2021 Mar;14(2):366-376. (PMID: 32814824)
Front Immunol. 2016 Jan 06;6:620. (PMID: 26779180)
Adv Immunol. 2015;127:203-56. (PMID: 26073985)
J Allergy Clin Immunol. 1994 Dec;94(6 Pt 2):1142-6. (PMID: 7798551)
Elife. 2019 May 14;8:. (PMID: 31084709)
Nat Rev Immunol. 2007 Apr;7(4):255-66. (PMID: 17380156)
J Clin Invest. 2019 Mar 1;129(3):1387-1401. (PMID: 30645205)
Cells. 2020 Dec 24;10(1):. (PMID: 33374255)
فهرسة مساهمة: Keywords: IgE receptor; Siglec-8; intracellular signaling; mast cells; proteomics
المشرفين على المادة: 0 (Antigens, CD)
0 (Antigens, Differentiation, B-Lymphocyte)
0 (Lectins)
0 (Receptors, IgE)
0 (SIGLEC8 protein, human)
EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
تواريخ الأحداث: Date Created: 20220214 Date Completed: 20220328 Latest Revision: 20220328
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC8837033
DOI: 10.3389/fimmu.2022.833728
PMID: 35154156
قاعدة البيانات: MEDLINE
الوصف
تدمد:1664-3224
DOI:10.3389/fimmu.2022.833728