Modulation of FcεRI-dependent mast cell response by OX40L via Fyn, PI3K, and RhoA

The Journal of Allergy and Clinical Immunology
Riccardo SibilanoCarlo Pucillo

Abstract

The interaction of mast cells (MCs) with regulatory T cells through the OX40 ligand (OX40L):OX40 axis downregulates FcεRI-dependent immediate hypersensitivity responses both in vitro and in vivo. Little is known on OX40L-mediated intracellular signaling or on the mechanism by which OX40L engagement suppresses MC degranulation. We explored the role of OX40L engagement on IgE/antigen-triggered MCs both in vitro and in vivo. The soluble form of OX40 molecule was used to selectively trigger OX40L on MCs in vitro and was used to dissect OX40L contribution in an in vivo model of systemic anaphylaxis. OX40L:OX40 interaction led to the recruitment of C-terminal src kinase into lipid rafts, causing a preferential suppression of Fyn kinase activity and subsequent reduction in the phosphorylation of Gab2, the phosphatidylinositol 3-OH kinase regulatory subunit p85, and Akt, without affecting the Lyn pathway. Dampening of Fyn kinase activity also inhibited RhoA activation and microtubule nucleation, key regulators of MC degranulation. The in vivo administration of a blocking antibody to OX40L in wild-type mice caused enhanced immediate hypersensitivity, whereas the administration of soluble OX40 to regulatory T-cell-depleted or OX40-defici...Continue Reading

References

May 17, 1991·Journal of Immunological Methods·M KarolF Vaughan
Jan 1, 1995·Current Biology : CB·L S PriceA Koffer
Jan 1, 1997·Annual Review of Cell and Developmental Biology·S M Thomas, J S Brugge
Jun 29, 2002·Nature Immunology·Valentino ParraviciniJuan Rivera
Jun 3, 2004·The Journal of Experimental Medicine·Sandra OdomJuan Rivera
Dec 22, 2005·Nature Medicine·Mohamed Bentires-AljHaihua Gu
Apr 19, 2006·The Journal of Experimental Medicine·Martina KovarovaJuan Rivera
Jun 6, 2006·The Journal of Allergy and Clinical Immunology·Juan Rivera, Alasdair M Gilfillan
Jul 13, 2006·The Journal of Biological Chemistry·Ido BacheletFrancesca Levi-Schaffer
Feb 13, 2007·European Journal of Immunology·Anna Katharina SimonAwen Gallimore
Mar 29, 2008·Annual Review of Immunology·Blayne A SayedMelissa A Brown
Oct 22, 2008·Nature Immunology·Janet Kalesnikoff, Stephen J Galli
Mar 18, 2009·Immunological Reviews·Alasdair M Gilfillan, Juan Rivera
Mar 26, 2009·Nature Reviews. Immunology·Michael Croft
Apr 8, 2009·The Journal of Allergy and Clinical Immunology·Cezmi A Akdis, Mübeccel Akdis
Oct 16, 2009·Current Opinion in Immunology·Martin Metz, Marcus Maurer
Nov 17, 2009·Immunological Reviews·Damiana Alvarez-ErricoJuan Rivera
Mar 24, 2010·Annual Review of Immunology·Michael Croft
Oct 19, 2011·Developmental and Comparative Immunology·Revathi Shanmugasundaram, Ramesh K Selvaraj

❮ Previous
Next ❯

Citations

Jan 29, 2013·The Journal of Allergy and Clinical Immunology·Bruce S BochnerFred Finkelman
Mar 25, 2014·Molecular Immunology·Riccardo SibilanoGiorgia Gri
Mar 31, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Nobuhiro NakanoHideoki Ogawa
Mar 31, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Vadym SulimenkoPavel Dráber
May 2, 2020·Clinical & Translational Immunology·Yan ZhangPeisong Gao
Aug 31, 2021·Frontiers in Immunology·Chiara Tontini, Silvia Bulfone-Paus
Oct 1, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Naeem KhanThomas L Rothstein

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.

Anaphylaxis

Anaphylaxis is a serious allergic reaction that is rapid in onset and may cause death.