一項(xiàng)最新的研究證實(shí)，人類 Tyk2基因的缺失以及相關(guān)訊息分子的不足,，將導(dǎo)致多重細(xì)胞激素的異常,，而影響人類正常的免疫反應(yīng)。
據(jù)了解這個(gè)由東京醫(yī)科與齒科大學(xué) (Tokyo Medical and Dental University)研究人員所參與的研究計(jì)劃,，原本把研究目標(biāo),，鎖定在罕見的高免疫球蛋白 E癥候群(Hyper IgE syndrome) 身上。參與的科學(xué)家發(fā)現(xiàn),，這類病人的癥狀,，和介白素12(IL-12) 以及干擾素(IFN) 異常的癥狀相當(dāng)?shù)念愃疲蚨l(fā)現(xiàn)了病人身上的Tyk2基因,，都帶有一個(gè)特定的基因突變,，而據(jù)先前相關(guān)的研究了解， Tyk2分子是個(gè)非受體型式酪氨酸激活酵素 (a non-receptor tyrosine kinase)的一個(gè)分子,，在代謝分類的族群中它屬于 Janus家族 (Jak family)的成員,，除此之外研究人員深入的追查這個(gè)突變所造成的影響，還意外的發(fā)現(xiàn)該突變,，還會導(dǎo)致了介白素 6(IL-6),、介白素10(IL-10) 、介白素23(IL-23)的活動異常,。
研究人員把這份研究成果,，發(fā)表在最新一期免疫學(xué) (Immunity)期刊上，而這個(gè)研究因此證實(shí)了,，Tyk2 基因特定 位點(diǎn)的突變,，影響了Tyk2分子的活動，因而牽連了 Jak激活酵素家族分子所參與的訊息傳遞路徑,，影響了多重免疫分子的代謝行為,。
英文原文：
Mouse model underestimates the critical role of Tyk2 in human immune system
A new study identifies a human Tyk2 deficiency and definitively links this molecule with multiple cytokine signals that are critical for the human immune responses. The research, published online in October 2006 by the journal Immunity, highlights the importance of Tyk2 function in humans and its differences in mice.
Dr. Yoshiyuki Minegishi from Tokyo Medical and Dental University and colleagues investigated immunological abnormalities in a patient diagnosed with a unique primary immunodeficiency called hyper IgE syndrome (HIES). The researchers observed that the patient showed some symptoms not frequently associated with HIES and found that the signaling pathways of two different soluble proteins (cytokines), IL-12 and IFN-? were defective in the patient. The researchers subsequently discovered that the patient carried a mutation in both copies of the gene for Tyk2. Tyk2, a non-receptor tyrosine kinase that belongs to the Janus kinase (Jak) family, is an enzyme shared by both IL-12 and IFN-?signaling pathways.
Surprisingly, the patient's cells displayed severe defects in signaling pathways not only for IL-12 and IFN-?but also for other cytokines including IL-6, IL-10 and IL-23, an observation that is in stark contrast to earlier studies with Tyk2-deficient mice that exhibited partially impaired IFN signaling and normal IL-6 and IL-10 signaling. This discrepancy is most likely due to a species difference between humans and mice. When normal Tyk2 was given to the patient's cells, it restored IL-12 and type I IFN signaling. In contrast, inhibition of Tyk2 expression in a normal human cell line disrupted IFN-?signaling. Therefore, unlike what has been observed in mice, Tyk2 appears to be critical for the multiple cytokine signals involved in the immune system in humans.
The researchers conclude that the absence of functional Tyk2 caused the defects in the multiple cytokine signals that were observed in the patient and identify human Tyk2 mutation as a unique type of primary immunodeficiency with characteristics similar to autosomal recessive HIES. "This study is the first to identify human Tyk2 deficiency and demonstrates the unique and indispensable role played by Tyk2 in the innate and acquired immune response in human," says Dr. Minegishi.
