Targeting SIRP-α 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 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.
Centre Hospitalier de l'Université de Montréal, Research Center CRCHUM, Montréal, QC, Canada.
Marianne
M
Raymond
Vu Quang
VQ
Van
Manuel
M
Rubio
Karl
K
Welzenbach
Marika
M
Sarfati
D019264:Adoptive Transfer; D000818:Animals; D001853:Bone Marrow / Q000473:pathology; D051928:CD47 Antigen / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology*
D051928:CD47 Antigen; D007141:Immunoglobulin Fc Fragments; C501922:Sirpa protein, mouse; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; D007073:Immunoglobulin E; D010047:Ovalbumin