IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.
IL25 elicits a multipotent progenitor cell population that promotes T(H)2 cytokine responses.
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CD4pos T辅助细胞(Th)2细胞分泌IL-4、IL-5和IL-13，是抵抗胃肠道蠕虫感染所必需的。然而，Th2细胞也促进与哮喘和过敏性疾病相关的慢性炎症。非造血细胞来源的细胞因子胸腺基质淋巴生成素(TSLP)、IL-33和IL-25(IL-17E)在粘膜部位引起Th2细胞依赖性炎症，但这些细胞因子如何影响先天免疫反应尚不清楚。在这里，我们展示了IL-25，IL-17细胞因子家族的成员，促进谱系阴性(Linneg)多能祖细胞(MPP)在肠道相关淋巴组织(GALT)中积累，从而促进Th2细胞因子反应。IL-25诱导的细胞群，称为MPPtype2细胞，由Sca-1的表达和c-kit(c-kitint)的中间表达定义，并具有多潜能，在体外和体内均可产生单核/巨噬细胞和粒细胞系。MPPtype2细胞的后代是合格的抗原提呈细胞，过继转移MPPtype2细胞可促进Th2细胞因子应答，并对正常易感的IL17e-/-小鼠产生保护性免疫。IL-25诱导MPP2型细胞群出现的能力确定了IL-17细胞因子家族与髓外造血之间的联系，并暗示了一种先前未知的先天免疫途径，促进粘膜部位的Th2细胞因子反应。
CD4pos T helper (Th) 2 cells secrete interleukin (IL)-4, IL-5 and IL-13 and are required for immunity to gastrointestinal helminth infections. However, Th2 cells also promote chronic inflammation associated with asthma and allergic disorders. The non-hematopoietic cell-derived cytokines thymic stromal lymphopoietin (TSLP), IL-33 and IL-25 (IL-17E) have been implicated in inducing Th2 cell-dependent inflammation at mucosal sites, but how these cytokines influence innate immune responses remains poorly defined. Here we show that IL-25, a member of the IL-17 cytokine family, promotes the accumulation of a lineage negative (Linneg) multi-potent progenitor (MPP) cell population in the gut-associated lymphoid tissue (GALT) that promotes Th2 cytokine responses. The IL-25-elicited cell population, termed MPPtype2 cells, was defined by expression of Sca-1 and intermediate expression of c-kit (c-kitint) and exhibited multi-potent capacity, giving rise to cells of monocyte/macrophage and granulocyte lineages both in vitro and in vivo. Progeny of MPPtype2 cells were competent antigen presenting cells and adoptive transfer of MPPtype2 cells could promote Th2 cytokine responses and confer protective immunity to helminth infection in normally susceptible Il17e-/- mice. The ability of IL-25 to induce the emergence of an MPPtype2 cell population identifies a link between the IL-17 cytokine family and extramedullary hematopoiesis and suggests a previously unrecognized innate immune pathway that promotes Th2 cytokine responses at mucosal sites.
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