探討 Syk 磷酸激酶在腸道表皮細胞中調控多聚免疫球蛋白受體之角色

Abstract

多聚免疫球蛋白受體 (polymeric immunoglobulin receptor, pIgR) 表現在腸道表皮細胞中，其對於維持腸道免疫系統的恆定扮演相當重要的角色，主要功能為協助免疫球蛋白 (Immunoglobulin A, IgA) 轉變成為分泌型免疫球蛋白(Secretory immunoglobulin A, sIgA)，並協助運送至腸道中，幫助維持腸道系統恆定。腸道表皮細胞會受到多種不同的刺激而增加多聚免疫球蛋白受體的表現，包含類鐸配體 (Toll-like receptor ligand)、介白素-17(Interleukin17, IL-17)、腫瘤壞死因子 (Tumor necrosis factor alpha, TNF-α)等等。 脾酪胺酸激酶 (Spleen tyrosine kinase, Syk) 在免疫細胞中已有許多研究指出其在訊號傳遞中扮演重要角色，但在腸道表皮細胞中的角色尚未有深入地探討。過去曾有報導指出，在以脾酪氨酸激酶抑制劑治療發炎性疾病時，會導致腹瀉的副作用。而脾酪胺酸激酶在免疫細胞以及部分非免疫細胞中會參與在介白素-17、腫瘤壞死因子、以及類鐸配體等之訊號傳遞過程，但在腸道表皮細胞上仍未有相關研究，因此本研究即是探討脾酪胺酸激酶是否可能會參與並影響在腸道表皮細胞中多聚免疫球蛋白受體的表現。 實驗中發現，在給予腸道表皮細胞介白素-17、腫瘤壞死因子-α 等的刺激之後，降低脾酪氨酸激酶會影響部分多聚免疫球蛋白受體的蛋白質的表現量。

Polymeric immunoglobulin receptor (pIgR) expressed in intestinal epithelial cells, which plays an essential role to maintain the homeostasis of the gut system. The main function of pIgR is to facilitate immunoglobulin A (IgA) transform to secretory immunoglobulin A (SIgA) and transport from lamina propria to lumen. Intestinal epithelial cells are regulated by different stimulations to upregulate the expression of pIgR, which included toll-like receptors (TLRs), interleukin-17 (IL-17), tumor necrosis factor-alpha (TNF-α). Spleen tyrosine kinase (Syk)has been reported to participate in different and abundant signaling transduction, but the role of Syk in intestinal epithelial cells remains unclear. Syk has been reported to participate in the signal transduction of IL-17, TLRs, and TNF in immune and nonimmune cells, however not on intestinal epithelia. Hence we hypothesized that Syk may participate and influence the expression of pIgR and affect the homeostasis of the gut system. In this study, we found that Syk may have participated in the regulation of pIgR expression, but need further experiment to confirm the effect of Syk in pIgR regulation.