Permanent cure strategy of inflammatory bowel diseases by inducing immunological reset

尽管“恶性”白血病可以通过骨髓移植治愈的时代已经到来，但“良性”炎症性肠病（IBD）仍然是难以治愈的终身疾病。我们发现，IBD中形成了记忆疾病的免疫记忆T细胞，并将其视为“良性T细胞白血病”样的终身病理，扩散到全身。我们证明，白细胞介素-7（IL-7）和共生菌是IBD中维持和增殖结肠炎CD4^+记忆T细胞必不可少的生存因子。尽管IL-17A被认为优先由T_h17细胞产生，并在自身免疫性疾病的发展中发挥关键作用，但它似乎在某些情况下抑制T_h1细胞的发展。在体内炎症条件下，结肠炎T_h1细胞和T_h17细胞似乎相互干扰。至少在炎症条件下，结肠炎的T_h1细胞和T_h17细胞不是独立产生的；相反，从T_h17到Th1细胞的线性顺序发育途径似乎占主导地位。尚需进一步研究，以确定由幼稚T细胞以不依赖rorγ T的方式直接产生的经典T_h1细胞是否也参与IBD的发病机制。从T_h17/T_h1细胞到替代的T_h1细胞的通路被T_<reg>细胞抑制，导致T_h17细胞被T_<reg>细胞积累。

Despite the advent of an age when "malignant" leukemia is cured by bone marrow transplantation, "benign" inflammatory bowel diseases(IBD) are still intractable lifelong diseases. We showed that immune memory T cells that remember the disease are formed in IBD, and perceiving them as "benign T-cell leukemia"-like lifelong pathology that spreads throughout the body, We demonstrated that interleukin-7(IL-7) and commensal bacteria are essential as a survival factor for the maintenance and proliferation of colitogenic CD4^+memory T cells, in IBD. Although IL-17A is thought to be preferentially produced by T_h17 cells and to play a critical role in autoimmune disease development, it seems to inhibit development of T_h1 cells in some circumstances. Colitogenic T_h1 cells and T_h17 cells seem to interfere with each other in vivo under inflammatory conditions. At least in inflammatory conditions, colitogenic T_h1 cells and T_h17 cells are not independently generated ; rather the linear sequential developmental pathway from T_h17 to Th1 cells seems to dominate. Further study is needed to determine whether the classical T_h1 cells directly generated from naive T cells in an RORγt-independent manner are also involved in IBD pathogenesis. The pathway from T_h17/T_h1 cells to alternative T_h1 cells is suppressed by T_<reg> cells, resulting in the accumulation of T_h17 cells by T_<reg> cells.