一项最新的研究证实，人类 Tyk2基因的缺失以及相关讯息分子的不足，将导致多重细胞激素的异常，而影响人类正常的免疫反应。
据了解这个由东京医科与齿科大学 (Tokyo Medical and Dental University)研究人员所参与的研究计划，原本把研究目标，锁定在罕见的高免疫球蛋白 E症候群(Hyper IgE syndrome) 身上。参与的科学家发现，这类病人的症状，和介白素12(IL-12) 以及干扰素(IFN) 异常的症状相当的类似，因而发现了病人身上的Tyk2基因，都带有一个特定的基因突变，而据先前相关的研究了解， Tyk2分子是个非受体型式酪氨酸激活酵素 (a non-receptor tyrosine kinase)的一个分子，在代谢分类的族群中它属于 Janus家族 (Jak family)的成员，除此之外研究人员深入的追查这个突变所造成的影响，还意外的发现该突变，还会导致了介白素 6(IL-6)、介白素10(IL-10) 、介白素23(IL-23)的活动异常。
研究人员把这份研究成果，发表在最新一期免疫学 (Immunity)期刊上，而这个研究因此证实了，Tyk2 基因特定 位点的突变，影响了Tyk2分子的活动，因而牵连了 Jak激活酵素家族分子所参与的讯息传递路径，影响了多重免疫分子的代谢行为。
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.
