2011 Fiscal Year Final Research Report
Elucidation of Molecular Mechanisms of Hyper-IgE Syndrome
| Project Area | Immunological Self Recognition and its Disorders |
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| Project/Area Number |
22021015
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| Research Category |
Grant-in-Aid for Scientific Research on Priority Areas
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
MINEGISHI Yoshiyuki 東京医科歯科大学, 大学院・医歯学総合研究科, 准教授 (10343154)
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| Project Period (FY) |
2010 – 2011
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| Keywords | 免疫不全症 / 高IgE症候群 / アトピー性疾患 / 高IgE血症 / 黄色ブドウ球菌 |
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| Research Abstract |
Hyper-IgE syndrome is a primary immunodeficiency characterized by recurrent staphylococcal infections and atopic dermatitis associated with elevated serum IgE levels. While defective Th17 cell differentiation partly accounts for susceptibility to staphylococcal skin abscesses and pneumonia, the pathogenesis of atopic manifestations in HIES still remains an enigma. Here we examined the differentiation and function of Th1, Th2, regulatory T (Treg), and dendritic cells in HIES patients carrying either STAT3 mutation. Although the in vitro differentiation of Th1/Th2 cells and the number and function of Treg cells in the peripheral blood were normal in HIES patients with STAT3 mutations, primary and monocyte-derived DCs showed defective response to IL-10 and hence failed to become tolerogenic. When treated with IL-10, patient DCs showed impaired upregulation of inhibitory molecules on their surface, including PD-L1 and ILT-4, compared to control DCs. Moreover, IL-10-treated DCs from patients displayed little ability to induce the differentiation of naive CD4 + T cells to FOXP3 + induced Treg cells that could suppress the proliferation and cytokine production of other CD4 + T cells. These results suggest that the defective generation of IL-10-induced tolerogenic DCs and iTreg cells might contribute, at least in part, to the development of atopic manifestations in HIES.
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[Journal Article] Defective IL-10 signaling in hyper-IgE syndrome results in impaired generation of tolerogenic dendritic cells and induced regulatory T cells.2011
Author(s)
Saito M, Nagasawa M, Takada H, Hara T, Tsuchiya S, Agematsu K, Yamada M, Kawamura N, Ariga T, Tsuge I, Nonoyama S, Karasuyama H, Minegishi Y.
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Journal Title
J Exp Med
Volume: 208
Pages: 235-249
Peer Reviewed
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[Journal Article] Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks.2010
Author(s)
Wada T, Ishiwata K, Koseki H, Ishikura T, Ugajin T, Ohnuma N, Obata K, Ishikawa R, Yoshikawa S, Mukai K, Kawano Y, Minegishi Y, Yokozeki H, Watanabe N, Karasuyama H.
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Journal Title
J Clin Invest.
Volume: 120
Pages: 2867-2875
Peer Reviewed
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