Involvement of CD300a Phosphatidylserine Immunoreceptor in Aluminum Salt Adjuvant-Induced Th2 Responses.
Aluminum salt (alum) has been widely used for vaccinations as an adjuvant. Alum not only enhances immunogenicity but also induces Th2 cell immune responses. However, the mechanisms of how alum enhances Th2 cell immune responses have been controversial. In an experimental allergic airway inflammation model, in which alum in conjunction with OVA Ag was i.p. injected for immunization, we found that apoptotic cells and inflammatory dendritic cells (iDC) expressing CD300a, an inhibitory immunoreceptor for phosphatidylserine (PS), significantly increased in number in the peritoneal cavity after the immunization. In contrast, apoptotic cells and iDCs were scarcely observed in the peritoneal cavity after injection of OVA alone. In CD300a-deficient mice, eosinophil infiltration in bronchoalveolar lavage fluid, serum IgE levels, and airway hyperreactivity were significantly decreased after immunization with alum plus OVA compared with wild-type mice. In vitro, iDCs purified from CD300a-deficient mice after the immunization induced significantly less IL-4 production from OT-II naive CD4(+) T cells after coculture with OVA Ag. CD300a expressed on iDCs bound PS on apoptotic cells in the peritoneal cavity after injection of OVA plus alum. Blocking CD300a interaction with PS by injection of a neutralizing anti-CD300a Ab resulted in inhibition of the development of allergic airway inflammation. These results suggest that CD300a is involved in alum-induced Th2 skewing.
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;
Haruka
H
Miki
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;
Chigusa
C
Nakahashi-Oda
Department of Internal Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan;
Takayuki
T
Sumida
Department of Immunology, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; Life Science Center of Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan; and Japan Science and Technology Agency, Core Research for Evolutional Science and Technology, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan ashibuya@md.tsukuba.ac.jp.
Akira
A
Shibuya
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000534:Alum Compounds / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001249:Asthma / Q000235:genetics / Q000276:immunology / Q000628:therapy; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D004804:Eosinophils / Q000276:immunology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010047:Ovalbumin / Q000494:pharmacology*; D010718:Phosphatidylserines / Q000037:antagonists & inhibitors; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000517:prevention & control; D018418:Th2 Cells / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D057134:Antibodies, Neutralizing; C476771:LMIR1 protein, mouse; D010718:Phosphatidylserines; D011971:Receptors, Immunologic; C446402:ovalbumin-alum; D015847:Interleukin-4; D007073:Immunoglobulin E; D010047:Ovalbumin