更快，更高，更强：开启更加给力免疫反应的蛋白质

2014年6月11日讯 /生物谷BIOON/ －－人体在首次受到病原体感染时给的免疫应答反应是缓慢而且是低烈度的，然而当人体再次受到该病原体感染，人体将会启动记忆细胞来进行高烈度，迅速的免疫应答反应。最近，Wistar研究所的研究人员发现，一种名为Foxp1的蛋白是抗体应答免疫反应过程中非常重要的组分。对该蛋白施加作用将为治疗免疫疾病开拓新的视野。Foxp1在免疫应答过程中的主要作用是协助激活CD4 T细胞，从而加强B细胞产生抗体以进行免疫反应。因此Foxp1蛋白是一种T细胞调控因子。受到Foxp1调控的T细胞是一种称为T Follicular Helper （TFH）的免疫T细胞，该类T细胞的主要功能是激活效应B细胞高烈度，和长效的免疫应答反应。Foxp1蛋白具有DNA结合位点，可以调控T细胞内基因的表达。因此，对Foxp1的抑制或者激活可以用来对免疫疾病和感染疾病进行治疗。该研究成果发表在了最新一期的Nature Immunology杂志上。

详细英文报道：

Your first response to an infectious agent or antigen ordinarily takes about a week, ａnd is relatively weak. However, if your immune system encounters that antigen a second time, the so-called memory response is rapid, powerful, ａnd very effective.

Now, a team of researchers at The Wistar Institute offers evidence that a protein, called Foxp1, is a key component of these antibody responses. Manipulating this protein＇s activity, they say, could provide a useful pathway to boosting antibody responses to treat infectious diseases, for example, or suppressing them to treat autoimmune disorders. Their findings appear online in the journal Nature Immunology.

"Foxp1 has an important role in our antibody immune responses, ａnd if we could find a way to regulate Foxp1 activity in a subset of T cells, the CD4+ T cells, it could have some profound impact on the antibody responses," said Hui Hu, Ph.D., senior author of the study ａnd associate professor at Wistar＇s National Cancer Institute-designated Cancer Center.

"Repressing Foxp1 activity, for example, we may be able to make antibody responses faster-acting ａnd more effective, which could be crucial in, say, a pandemic when time is a critical factor," Hu said. "Alternatively, if we could enhance the effectiveness of this protein, we may be able to significantly dampen the antibody responses that are unwanted in some cases of autoimmune diseases such as lupus."

Previously, the Hu laboratory determined that Foxp1 was responsible for keeping T cells －－ the white blood cells that mediate our immune system －－ on "active stand-by mode," a process called quiescence. In the present study, Hu teamed with the laboratories of Louise C. Showe, Ph.D., professor in the Wistar Cancer Center＇s Molecular ａnd Cellular Oncogenesis program, which provided crucial genomics expertise, ａnd Jan Erickson, Ph.D., professor in the Tumor Microenvironment ａnd Metastasis program, which offered expertise in the study of autoimmunity ａnd the activation of B cells, the cells that generate antibodies.

According to their Nature Immunology report, variants （or isoforms） of Foxp1 （called Foxp1A ａnd Foxp1D） are critical regulators for the formation of a type of T cells, called T Follicular Helper （TFH） cells. These TFH cells then go on to enable B cells in creating long-lived, highly reactive antibodies. The proteins are transcription factors, meaning they work by binding to DNA to control which genes in these T cells are "read" or translated into protein.

In the initial days of an immune response, the Foxp1 proteins determine how TFH cells arise from activated T cells. "The two isoforms act as regulators of TFH differentiation in the early moments of the immune response, where they effectively act as gatekeepers to slow TFH development, " Hu said. "They constitute a ＇double-check＇ system that prevents the humoral branch of the immune system from acting too hastily."

原创作者：上海义森生物科技有限公司