自體免疫調節因子

自體免疫調節因子（Autoimmune regulator）是人體內由AIRE基因表現的蛋白質。AIRE是在胸腺髓質表現的轉錄因子，使人體不會被自身的免疫系統攻擊。 每個T細胞都會辨識由抗原呈現細胞上MHC分子複合體呈現的特定抗原，这一识别需要T細胞表面的T細胞受体。T細胞受体由VDJ重組片段所製造，所以T細胞多樣性很高，而每個T細胞都有專一性。接著，會辨識自身蛋白質的T細胞受器必須在還在胸腺內時消除。透過AIRE作用，胸腺髓質上皮細胞（mTEC）會表現身體其他各個地方的主要蛋白質（所謂的 TRA），而且將會和這些蛋白質反應的T細胞透過細胞程序性死亡（细胞凋亡）的方式消除。因此AIRE針對自體辨識的T細胞進行負向篩選（英语：Negative selection (immunology)）。當AIRE受損時，會辨識人體自身抗原的T細胞會離開胸腺，進入血液循環，並可能導致許多的自體免疫疾病。 在胸腺中，AIRE會促進一個大範圍的特定器官基因的轉錄，並製造出只在周邊組織表現的蛋白質，在胸腺中創造｢免疫的影子｣透過負向篩選（英语：Negative selection (immunology)），將在胸腺中會和自身抗原強烈結合的T細胞消除是很重要的，否則之後他們可能會遇到能強烈結合的自身抗原，引發自體免疫反應。所以在胸腺內藉由AIRE表現非當地的蛋白質，消除和自身抗原反應的T細胞，可以降低自體免疫的威脅。再者，AIRE被發現會在次級淋巴組織中一群間質細胞中表現，然而這些細胞表現出的TRAs和mTECs所表現出的不同。。 基因改造鼠相關的研究指出AIRE藉由在胸腺內啟動多樣的自身抗原（例如：胰島素）的轉錄而作用。這個表現允許成熟中的胸腺細胞對周邊器官展現耐受性，進而抑制自體免疫疾病。 AIRE基因亦會在很多其他組織中表現。AIRE也會在老鼠中的33D1+的樹突細胞及人類樹突細胞。 AIRE基因突變發生於一種罕見的自體免疫疾病，APS-1(Autoimmune Polyendocrinopathy Syndrome type 1)，又稱作APECED( Autoimmune Polyendocrinopathy-Candidiasis-Ectodermal Dystrophy)。AIRE的阻斷會產生許多自體免疫疾病，臨床上最常見的案例是甲狀旁腺功能減退症（英语：Hypoparathyroidism）、原發性腎上腺皮質功能衰竭（英语：Adrenal insufficiency）和慢性黏膜皮膚念珠菌病（英语：Chronic mucocutaneous candidiasis）。 為了探討人類的疾病機制，會使用剔除AIRE基因的轉基因小鼠模型來進行研究。 免疫系统 免疫耐受 與自體免疫調節因子相關的疾病；在維基數據上查看/編輯參考.  GRCh38: Ensembl release 89: ENSG00000160224 - Ensembl, May 2017 GRCm38: Ensembl release 89: ENSMUSG00000000731 - Ensembl, May 2017 Human PubMed Reference:. 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