TY - JOUR
T1 - Selective suppression of oral allergen-induced anaphylaxis by Allergin-1 on basophils in mice
AU - Lin, Yu Hsien
AU - Tahara-Hanaoka, Satoko
AU - Nagai, Kei
AU - Yoshikawa, Soichiro
AU - Kubo, Masato
AU - Shibayama, Shiro
AU - Karasuyama, Hajime
AU - Shibuya, Akira
N1 - Funding Information:
This work was supported in part by grants provided by the Japan Society for the Promotion of Science (KAKENHI) (grant numbers 16H06387 and 18H05022 to A.S.) and Ono Pharmaceutical Company Ltd.
Funding Information:
Conflicts of interest statement: This research was funded in part by Ono Pharmaceutical Co., Ltd. S.S. is an employee of Ono Pharmaceutical Co., Ltd. The sponsor had no control over the interpretation, writing or publication of this work.
Publisher Copyright:
© 2019 The Japanese Society for Immunology. All rights reserved.
PY - 2019/12/3
Y1 - 2019/12/3
N2 - Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcϵRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas-TRECK mice, which had been reconstituted with either WT or Milr1-/- bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1-/- mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.
AB - Mast cells (MCs) play a critical role in oral allergen-induced anaphylaxis. However, the contribution of basophils to the anaphylaxis remains unclear. The inhibitory immunoreceptor Allergin-1 is highly expressed on MCs and basophils and inhibits FcϵRI-mediated signaling in MCs. Here, we show that Allergin-1-deficient (Milr1-/-) mice developed more severe hypothermia, a higher mortality rate and a greater incidence of diarrhea than did wild-type (WT) mice in an oral ovalbumin (OVA)-induced food allergy model. MC-deficient Mas-TRECK mice, which had been reconstituted with either WT or Milr1-/- bone marrow-derived cultured MCs, did not develop hypothermia in this food allergy model. On the other hand, depletion of basophils by injection of anti-CD200R3 antibody rescued Milr1-/- mice from lethal hypothermia but not from diarrhea. In vitro analyses demonstrated that Allergin-1 inhibits IgE-dependent activation of both human and mouse basophils. Thus, Allergin-1 on basophils selectively suppresses oral allergen-induced anaphylaxis.
KW - diarrhea
KW - food allergy
KW - mast cells
UR - http://www.scopus.com/inward/record.url?scp=85081893075&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85081893075&partnerID=8YFLogxK
U2 - 10.1093/intimm/dxz075
DO - 10.1093/intimm/dxz075
M3 - Article
C2 - 31793637
AN - SCOPUS:85081893075
SN - 0953-8178
VL - 32
SP - 213
EP - 219
JO - International Immunology
JF - International Immunology
IS - 3
ER -