Kitani A, Xu L
Mucosal Immunity Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland, USA.
Mucosal Immunol. 2008 Nov;1 Suppl 1:S43-6. doi: 10.1038/mi.2008.51.
T helper (Th)17 cells have been shown to play a role in the pathogenesis of inflammatory and autoimmune diseases including inflammatory bowel diseases (IBD). It is now well established that although transforming growth factor (TGF)-beta alone induces FoxP3(+) regulatory T (Treg) cells, TGF-beta and interleukin (IL)-6, acting in concert, induce differentiation of mouse naive T cells into Th17. As we previously showed that CD4(+)CD25(+)Foxp3(+) "natural" Treg cells express cell surface or secrete TGF-beta, we examined whether Treg cells serve to induce Th17 differentiation. We found that upon activation, Treg cells induce CD4(+)CD25(-) naive T cells or Treg cells themselves to differentiate into Th17 in the presence of IL-6 alone without exogenous addition of TGF-beta. We also found that TGF-â is also produced by dendritic cells that are in contact with Treg cells. Although Treg cells are effectively recruited at inflamed mucosa in patients with IBD, it is possible that Treg cells may have undesirable effects through their ability to differentiate into pathogenic Th17 in the presence of IL-6 and/or IL-23 at sites of inflammation. Further study of the relationship between Treg cells and Th17 cells in the inflamed tissue in IBD is important for possible Treg cell-mediated therapeutic applications.
辅助性T（Th）17细胞已被证明在包括炎症性肠病（IBD）在内的炎症和自身免疫性疾病的发病机制中发挥作用。目前已经明确，虽然单独的转化生长因子（TGF）-β可诱导FoxP3（+）调节性T（Treg）细胞，但TGF-β和白细胞介素（IL）-6协同作用可诱导小鼠幼稚T细胞分化为Th17。正如我们之前所表明的，CD4（+）CD25（+）Foxp3（+）“天然”Treg细胞表达细胞表面或分泌TGF-β，我们研究了Treg细胞是否有助于诱导Th17分化。我们发现，激活后，Treg细胞在仅存在IL-6而不额外添加外源性TGF-β的情况下，可诱导CD4（+）CD25（-）幼稚T细胞或Treg细胞自身分化为Th17。我们还发现，与Treg细胞接触的树突状细胞也会产生TGF-β。虽然在IBD患者的炎症黏膜中Treg细胞能有效募集，但在炎症部位，Treg细胞可能通过在IL-6和/或IL-23存在下分化为致病性Th17的能力而产生不良影响。进一步研究IBD炎症组织中Treg细胞与Th17细胞之间的关系对于可能的Treg细胞介导的治疗应用很重要。
