Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz and Research Center for Immunotherapy, Paul-Klein-Center for Immune Intervention, 55131 Mainz, Germany.
Institute for Immunology, University Medical Center of the Johannes Gutenberg-University Mainz and Research Center for Immunotherapy, Paul-Klein-Center for Immune Intervention, 55131 Mainz, Germany
J Immunol. 2021 Jan 1;206(1):67-76. doi: 10.4049/jimmunol.1900310. Epub 2020 Dec 2.
IL-9 has lent its numerical designation to the Th9 subset of CD4 Th cells, although it is also produced by additional cell types, including mast cells. It is a pleiotropic cytokine involved in allergic reactions, parasitic infections, autoimmune inflammation, and cancer immunity. In this article, we provide evidence that NFATc2 has contradictory functions in the expression of IL-9 in murine Th9 cells and bone marrow-derived mast cells (BMMC). The basis for this is our observation that the production of IL-9 in NFATc2-deficient Th9 cells is increased, whereas it is decreased in BMMC devoid of NFATc2. In addition, NFATc2 deficiency almost completely abrogates the expression of IL-3 in both cell types. However, selectively in BMMC, the production of IL-9 critically depends on autocrine IL-3 acting via the sustained activation of STAT5 on the expression of IL-9. Furthermore, we demonstrate that IL-3 acts independently and synergistically with IL-1β on the production of IL-9. Taken together, we highlight NFATc2-driven production of autocrine IL-3 as a critical and cell type-specific component for IL-9 expression in BMMC.
IL-9 将其数字指定赋予了 CD4 Th 细胞的 Th9 亚群，尽管它也由其他细胞类型产生，包括肥大细胞。它是一种多效细胞因子，参与过敏反应、寄生虫感染、自身免疫炎症和癌症免疫。在本文中，我们提供了证据表明 NFATc2 在小鼠 Th9 细胞和骨髓来源的肥大细胞（BMMC）中 IL-9 的表达具有相反的功能。这是基于我们的观察，即在 NFATc2 缺陷型 Th9 细胞中，IL-9 的产生增加，而在缺乏 NFATc2 的 BMMC 中则减少。此外，NFATc2 缺陷几乎完全消除了这两种细胞类型中 IL-3 的表达。然而，在 BMMC 中，IL-9 的产生严重依赖于自分泌的 IL-3，通过 STAT5 的持续激活来表达 IL-9。此外，我们证明 IL-3 可独立并与 IL-1β 协同作用于 IL-9 的产生。总之，我们强调了 NFATc2 驱动的自分泌 IL-3 的产生，这是 BMMC 中 IL-9 表达的关键和细胞类型特异性组成部分。
