Transcription factor E3, a major regulator of mast cell-mediated allergic response

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:129

Article

Yagil, Zohar¹  Erlich, Tal Hadad¹  Ofir-Birin, Yifat¹  Tshori, Sagi²  Kay, Gillian¹  Yekhtin, Zanna³  Fisher, David E.⁵  Cheng, Chang⁶  Wong, W. S. Fred^6,7  Hartmann, Karin⁸  Razin, Ehud¹  Nechushtan, Hovav⁴ 

[1] Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem & Mol Biol, Inst Med Res Israel Canada, IL-91010 Jerusalem, Israel

[2] Hadassah Hebrew Univ, Dept Nucl Med, Med Ctr, Jerusalem, Israel

[3] Hadassah Hebrew Univ, Dept Bone Marrow Transplantat & Canc Immunotherap, Med Ctr, Jerusalem, Israel

[4] Hadassah Hebrew Univ, Dept Oncol, Med Ctr, Jerusalem, Israel

[5] Massachusetts Gen Hosp, Boston, MA 02114 USA

[6] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Pharmacol, Natl Univ Hlth Syst, Singapore 117595, Singapore

[7] Natl Univ Singapore, Program Immunol, Inst Life Sci, Singapore 117548, Singapore

[8] Univ Cologne, Dept Dermatol, Cologne, Germany

关键词: Allergy;    mast cells;    degranulation;    histamine;    cytokine secretion;    transcription factor E3 knockout mice;   

DOI  :  10.1016/j.jaci.2011.11.051

来源: Elsevier

【 摘 要 】

Background: Microphthalmia transcription factor, an MiT transcription family member closely related to transcription factor E3 (TFE3), is essential for mast cell development and survival. TFE3 was previously reported to play a role in the functions of B and T cells; however, its role in mast cells has not yet been explored. Objective: We sought to explore the role played by TFE3 in mast cell function. Methods: Mast cell numbers were evaluated by using toluidine blue staining. FACS analysis was used to determine percentages of Kit and Fc epsilon RI double-positive cells in the peritoneum of wildtype (WT) and TFE3 knockout (TFE3(-/-)) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In vivo plasma histamine levels were measured after immunologic triggering of these mice. Results: No significant differences in mast cell numbers between WT and TFE3(-/-) mice were observed in the peritoneum, lung, and skin. However, TFE3(-/-) mice showed a marked decrease in the number of Kit(+) and Fc epsilon RI+ peritoneal and cultured mast cells. Surface expression levels of FceRI in TFE3(-/-) peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3-/- mice showed a marked decrease in degranulation and mediator secretion. In vivo experiments showed that the level of plasma histamine in TFE3(-/-) mice after an allergic trigger was substantially less than that seen in WT mice. Conclusion: TFE3 is a novel regulator of mast cell functions and as such could emerge as a new target for the manipulation of allergic diseases. (J Allergy Clin Immunol 2012;129:1357-66.)

【 授权许可】

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