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

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• 作者：Zohar Yagil ; PhD^a ; Tal Hadad Erlich ; MSc^a ; Yifat Ofir-Birin ; MSc^a ; Sagi Tshori ; MD ; PhD^b ; Gillian Kay ; PhD^a ; Zanna Yekhtin ; BSc^c ; David E. Fisher ; MD ; PhD^d ; Chang Cheng ; PhD^e ; W. S. Fred Wong ; PhD^e ; ^f ; Karin Hartmann ; MD^g ; Ehud Razin ; PhD^a ; ^{ehudr@ekmd.huji.ac.il} ; Hovav Nechushtan ; MD ; PhD^h
• 关键词：Allergy ; mast cells ; degranulation ; histamine ; cytokine secretion ; transcription factor E3 knockout mice
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2012
• 期刊代码：158_00916749
• 类别：med
• 出版时间：May, 2012
• 卷：129
• 期：5
• 页码：1357-1366.e5
• 文件大小：1518 K

摘要

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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蔚RI double-positive cells in the peritoneum of wild-type (WT) and TFE3 knockout (TFE3^{鈭?鈭?/sup>) mice. Cytokine and inflammatory mediator secretion were measured in immunologically activated cultured mast cells derived from either knockout or WT mice. In聽vivo plasma histamine levels were measured after immunologic triggering of these mice.}

Results

No significant differences in mast cell numbers between WT and TFE3^{鈭?鈭?/sup> mice were observed in the peritoneum, lung, and skin. However, TFE3鈭?鈭?/sup> mice showed a marked decrease in the number of Kit+ and Fc蔚RI+ peritoneal and cultured mast cells. Surface expression levels of Fc蔚RI in TFE3鈭?鈭?/sup> peritoneal mast cells was significantly lower than in control cells. Cultured mast cells derived from TFE3鈭?鈭?/sup> mice showed a marked decrease in degranulation and mediator secretion. In聽vivo experiments showed that the level of plasma histamine in TFE3鈭?鈭?/sup> 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.