研究Galectins在Treg-of-B細胞的調控機轉上所扮演的角色

Abstract

Treg-of-B細胞是一群具有抑制能力的調節性T細胞，他們和其他調節性T細胞不同，不同於第一型調節性T細胞不同的地方在於Treg-of-B是一群CD25陽性的細胞，而第一型調節性T細胞則是CD25陰性，在轉錄因子Foxp3的表現上，Treg-of-B並不表現Foxp3，這個部分與自然調節性T細胞亦不相同，而目前為止，關於Treg-of-B的研究有限，所以我們希望能夠更加了解Treg-of-B在免疫抑制上的功能。半乳糖凝集素是一群會和-galactoside結合的蛋白，目前有愈來愈多文獻指出，他們和先天免疫與後天免疫之間都有相關性，例如半乳糖凝集素-2能夠造成CD8陽性T細胞的細胞凋亡來達到抑制免疫反應，但在先天免疫上，半乳糖凝集素卻扮演一個促進發炎的角色。 而從我們的實驗中發現，Treg-of-B會高度表現半乳糖凝集素-2的基因，而自然調節性T細胞的表現量則和naïve T cell相差不多，接著我們進一步研究半乳糖凝集素-2如何去抑制T細胞增生，於是藉由阻斷naïve T cell表面上半乳糖凝集素-2的可能結合受體CD29來看是否會影響半乳糖凝集素-2的抑制能力，而實驗結果發現，實驗組和對照組並無差異，我們推測半乳糖凝集素-2並非直接抑制T 細胞的增生，可能是藉由影響其他細胞激素來抑制T細胞的增生，先前研究指出半乳糖凝集素-1與介白素-10的合成有關，而我們利用介白素-10剔除小鼠的T細胞和一般小鼠的B細胞養出不會產生介白素-10的Treg-of-B細胞，經實驗發現剔除介白素-10的Treg-of-B細胞同樣具有抑制能力，而細胞相較於一般Treg-of-B細胞會表現較高的半乳糖凝集素-1，半乳糖凝集素-2和半乳糖凝集素-12，由此實驗結果可知，在沒有介白素-10的情況下，Treg-of-B細胞可能會轉錄更多的半乳糖凝集素基因，不過介白素-10和半乳糖凝集素之間的關係以及之間的機轉仍有待後續研究。

Regulatory T cells induced by B cells (Treg-of-B cells) are a subpopulation of regulatory T cells. They are different from other regulatory T cells. Compared to natural regulatory T cells, Treg-of-B cells are Foxp3 negative, and they are CD25 positive while type 1 regulatory T cells (Tr1 cells) are CD25 negative. However, Treg-of-B cells suppressive function is not clearly understood, so we aim to further investigate how Treg-of-B cells suppress immune responses. Galectins are -galactoside proteins, and there are many researches showing that galectins play roles in innate and adaptive immunity. For example, galectin-2 suppresses immune responses by inducing CD8+ T cells apoptosis. However, in innate immunity, galectin-2 induces a proinflammatory phenotype in monocytes and macrophages. We focused on the roles of galectins in Treg-of-B cells. We first checked the galectins gene expression in Treg-of-B cells by real-time PCR and found that galectin-2 was highly expressed in Treg-of-B cells while natural regulatory T cells express similar level as CD4+CD25- T cells. We further investigated the suppressive mechanism by blocking the possible binding partner of galectin-2, CD29. However, it showed no difference between the experimental group and control group. To check the blocking efficiency of anti-CD29, we found that galectin-2 could not suppress T cell directly, which suggested that galectin-2 might interact with other molecules to suppress T cell proliferation. It was reported that galectin-1 contributed to IL-10 synthesis. In our study, we found that not only galectin-1 mRNA expression increase, galectin-2 also express higher when IL-10 was deficient. More researches should be performed to clarify the correlation between galectins and IL-10.