Browse views: by Year, by Function, by GLF, by Subfunction, by Conference, by Journal

Targeting SIRP-α protects from type 2-driven allergic airway inflammation.

Van, VQ and Raymond, M and Baba, N and Wakahara, K and Martinez-Torres, AC and Santos, AS and Sarfati, M (2010) Targeting SIRP-α protects from type 2-driven allergic airway inflammation. Eur J Immunol..

Abstract

The interplay between innate and adaptive immune responses is essential for the establishment of allergic diseases. CD47 and its receptor, signal regulatory protein α (SIRP-α), govern innate cell trafficking. We previously reported that administration of CD47(+/+) but not CD47(-/-) SIRP-α(+) BM-derived DC (BMDC) induced airway inflammation and Th2 responses in otherwise resistant CD47-deficient mice. We show here that early administration of a CD47-Fc fusion molecule suppressed the accumulation of SIRP-α(+) DC in mediastinal LN, the development of systemic and local Th2 responses as well as airway inflammation in sensitized and challenged BALB/c mice. Mechanistic studies highlighted that SIRP-α ligation by CD47-Fc on BMDC did not impair Ag uptake, Ag presentation and Ag-specific DO11.10 Tg Th2 priming and effector function in vitro, whereas in vivo administration of CD47-Fc or CD47-Fc-pretreated BMDC inhibited Tg T-cell proliferation, pinpointing that altered DC trafficking accounts for defective Th priming. We conclude that the CD47/SIRP-α axis may be harnessed in vivo to suppress airway SIRP-α(+) DC homing to mediastinal LN, Th2 responses and allergic airway inflammation.

Item Type: Article
Keywords: CD47; SIRPa-Fc; Memory T cell, Effector T cell;
Date Deposited: 07 Jun 2016 23:45
Last Modified: 07 Jun 2016 23:45
URI: https://oak.novartis.com/id/eprint/5340

Search

Email Alerts

Register with OAK to receive email alerts for saved searches.