The Jackson Laboratory, Bar Harbor, ME, USA; Genetics Program, Sackler School of Graduate Biomedical Sciences, Tufts University, Boston, MA, USA.
The Jackson Laboratory, Bar Harbor, ME, USA.
Cell Rep. 2017 Oct 3;21(1):208-221. doi: 10.1016/j.celrep.2017.09.036.
Interleukin 21 (IL-21) plays key roles in humoral immunity and autoimmune diseases. It is known to function in mature CD4 T follicular B cell helper (T) cells, but its potential involvement in early T cell ontogeny is unclear. Here, we find that a significant population of newly activated thymic and peripheral CD4 T cells functionally expresses IL-21 soon after birth. This naturally occurring population, termed natural (n)T21 cells, exhibits considerable similarity to mature T cells. nT21 cells originating and activated in the thymus are strictly dependent on autoimmune regulator (AIRE) and express high levels of NUR77, consistent with a bias toward self-reactivity. Their activation/expansion in the periphery requires gut microbiota and is held in check by FoxP3 T cells. nT21 cells are the major thymic and peripheral populations of IL-21 cells to expand in an IL-21-dependent humoral autoimmune disease. These studies link IL-21 to T cell ontogeny, self-reactivity, and humoral autoimmunity.
白细胞介素 21 (IL-21) 在体液免疫和自身免疫性疾病中发挥关键作用。已知它在成熟的 CD4 滤泡辅助性 B 细胞 T 细胞 (T) 中发挥作用，但它在早期 T 细胞发生中的潜在作用尚不清楚。在这里，我们发现大量新激活的胸腺和外周 CD4 T 细胞在出生后不久就会功能性地表达 IL-21。这种自然存在的群体，称为天然 (n)T21 细胞，与成熟的 T 细胞具有相当大的相似性。起源于胸腺并被激活的 nT21 细胞严格依赖于自身免疫调节因子 (AIRE)，并表达高水平的 NUR77，这与自身反应性有关。它们在外周的激活/扩增需要肠道微生物群，并且受到 FoxP3 T 细胞的抑制。nT21 细胞是在依赖 IL-21 的体液自身免疫性疾病中扩增的主要胸腺和外周 IL-21 细胞群体。这些研究将 IL-21 与 T 细胞发生、自身反应性和体液自身免疫联系起来。
