探討Syk 在腸道表皮細胞中的介白素-22 訊息傳遞及功 能之角色

Abstract

脾酪氨酸激酶(spleen tyrosin kinase, Syk)在免疫細胞中的功能及表現已被廣泛研究，其中發現Syk參與許多細胞活化或是免疫反應的訊息傳遞路徑．也有一些研究指出Syk也存在於非免疫細胞中，但有關它在腸道表皮細胞中的角色及功能都還不清楚．腸道表皮細胞在維持腸道系統恆定中扮演重要的角色，若其功能異常可能導致發炎性腸道疾病(inflammatory bowel disease, IBD)．先前的研究發現在腸道表皮細胞專一性剔除Syk的小鼠（SykΔIEC）經葡聚糖硫酸鈉(dextran sulfate sodium, DSS)引發腸炎後，其發炎情形較野生型(WT)嚴重，似乎Syk在腸道表皮細胞中具有保護的功能．因此我們假設Syk參與腸道表皮細胞中的某種訊息傳遞路徑，因而影響表皮細胞的功能．根據先前的文獻指出介白素-22（Interleukin-22, IL-22）可促進腸道表皮細胞產生抗微生物胜肽(antimicrobial peptides, AMPs)及黏液蛋白(mucin)，進而減緩腸炎的情形; 而IL-22的訊息傳遞方式主要是經由活化JAK1/3-STAT3來調控細胞反應．因此我們將研究Syk是否參與在IL-22的訊息傳遞中．此篇研究我們探討Syk的確參與在IL-22-STAT3的訊息傳遞中，並可幫助腸道表皮細胞產生抗微生物胜肽及黏液蛋白，幫助維持腸道系統的恆定．

Spleen tyrosin kinase (Syk) is widely expressed in hematopoietic cells and regulates many immune responses. While Syk is also expressed in non- hematopoietic cells, the role of Syk in intestinal epithelial cells (IECs) is still elusive. IECs play an important role in maintaining mucosal homeostasis, so dysregulation of IECs causes the development of inflammatory Bowel disease (IBD). In previous study, we have demonstrated that IEC-specific Syk-deficient (SykΔIEC) mice are more sensitive to dextran sodium sulfate (DSS)-induced colitis compared to normal mice. Thus, we hypothesize that Syk may be involved in a protective signal in IECs. According to literature, interleukin 22 (IL-22) is known to reduce colitis through enhancing the production of antimicrobial peptides (AMPs) and mucin by IECs. These functions are mediated by activations of STAT3 and some kinases. In this study, we found that Syk may play a positive role in IL-22-STAT3 pathway and promoted secretion of AMPs and mucin in order to maintain gut homeostasis .