Targeting SIRP-[alpha] protects from type 2-driven allergic airway inflammation

The interplay between innate and adaptive immune responses is essential for the establishment of allergic diseases. CD47 and its receptor, signal regulatory protein [alpha] (SIRP-[alpha]), govern innate cell trafficking. We previously reported that administration of CD47+/+ but not CD47-/- SIRP-[alpha]+ 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-[alpha]+ 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-[alpha] 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-[alpha] axis may be harnessed in vivo to suppress airway SIRP-[alpha]+ DC homing to mediastinal LN, Th2 responses and allergic airway inflammation.