半乳糖凝集素-3在iNKT細胞產生的介白素-17中所扮演的角色

Abstract

半乳糖凝集素-3 (Galectin-3)是半乳糖凝集素家族的一員，含有能特定和半乳糖苷結合的編碼區 (CRD)。Galectin-3的功能十分多樣化，包含活化、黏附、細胞凋亡、細胞遷移和吞噬作用。 不變的自然殺手T細胞 (iNKT cell)的T細胞受體 (TCRs)會專一性地去辨認CD1d-α-GalCer複合體。經由CD1d-α-GalCer的刺激後，iNKT cell 會快速且大量地產生細胞激素 (cytokines)。這些由iNKT cell所產生的cytokines，經報導證實在許多過敏性、自體免疫及感染性疾病的致病過程中扮演重要的角色。雖然目前已知Galectin-3參與在人類疾病和免疫反應，但是Galectin-3在iNKT cell產生cytokines及細胞相關的發炎反應的影響尚未釐清。 在我們的研究中，我們首先檢驗Galectin-3是否有表現在iNKT cell中。我們發現Galectin-3在胰臟、腸繫膜淋巴結及周邊淋巴結的iNKT cell中皆有表現。 接下來我們使用野生型(WT)及半乳糖凝集素-3缺失型(Gal-3 KO)的小鼠，觀察在注射α-GalCer後iNKT cell的族群數量。我們得知Galectin-3的缺失並不會影響iNKT cell在胰臟、腸繫膜淋巴結及周邊淋巴結的族群數目。我們更進一步研究以體內施打α-GalCer以刺激小鼠，觀察其iNKT cell的細胞激素分佈型 (cytokine profile)。我們的結果顯示Galectin-3缺失的周邊淋巴結iNKT cell跟野生型比較顯著地分泌較少的介白素-17 (IL-17)。 研究結果指出Galectin-3在iNKT cell所調節的IL-17分泌中，扮演了正向的特定性角色。

Galectin-3 (gal-3), a member of the galectin family, contains CRD that enable the specific binding of β-galactosides. The functions of galectin-3 are diverse, including activation, adhesion, apoptosis, cell migration and phagocytosis. The T cell receptors (TCRs) of invariant NKT (iNKT) cells specifically recognize CD1d-α-GalCer complex. Upon activation by CD1d-α-GalCer, iNKT cells rapidly produce large amounts of cytokines. These cytokines produced by iNKT cells have been reported to play a crucial role in the pathogenesis of various allergic, autoimmune and infectious diseases. Although galectin-3 is involved in various human diseases and immune responses, its role in cytokine production by iNKT cells and the effect in iNKT cell-mediated inflammation remain unclear. In our study, we first examined whether galectin-3 is expressed by iNKT cells. We found that galectin-3 is expressed in iNKT cells from spleen (SP), mesenteric lymph nodes (mLNs) and peripheral lymph nodes (pLNs). We next used WT and Gal-3 KO mice to examine the population of iNKT cells after injection with α-GalCer. Deficiency of galectin-3 doesn’t affect the iNKT population in SP, mLN and pLN. We further studied the cytokine profile of iNKT cells after stimulation with α-GalCer in vivo. Our data indicated the galectin-3-deficent iNKT cells in pLN secret less IL-17 than WT iNKT cells. Our results suggest that the positive and specific role of galectine-3 in regulating IL-17 production by iNKT cells.