Department of Pediatrics and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, United States.
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Immunol. 2023 Feb 22;14:1026368. doi: 10.3389/fimmu.2023.1026368. eCollection 2023.
Bone marrow Treg cells (BM Tregs) orchestrate stem cell niches crucial for hematopoiesis. Yet little is known about the molecular mechanisms governing BM Treg homeostasis and function. Here we report that the transcription factor BATF maintains homeostasis and functionality of BM Tregs to facilitate homeostatic regulation of hematopoiesis and B cell development. Treg-specific ablation of BATF profoundly compromised proportions of BM Tregs associated with reduced expression of Treg effector molecules, including CD44, ICOS, KLRG1, and TIGIT. Moreover, BATF deficiency in Tregs led to increased numbers of hematopoietic stem cells (HSCs), multipotent progenitors (MPPs), and granulocyte-macrophage progenitors (GMPs), while reducing the functionality of myeloid progenitors and the generation of common lymphoid progenitors. Furthermore, Tregs lacking BATF failed to support the development of B cells in the BM. Mechanistically, BATF mediated IL-7 signaling to promote expression of effector molecules on BM Tregs and their homeostasis. Our studies reveal a previously unappreciated role for BATF in sustaining BM Treg homeostasis and function to ensure hematopoiesis.
骨髓 T 调节细胞（BM Tregs）调控着造血所必需的干细胞龛。然而，关于调控 BM Treg 稳态和功能的分子机制知之甚少。在这里，我们报告转录因子 BATF 维持 BM Treg 的稳态和功能，以促进造血和 B 细胞发育的稳态调节。Treg 特异性 BATF 缺失显著损害了与 Treg 效应分子表达降低相关的 BM Treg 的比例，包括 CD44、ICOS、KLRG1 和 TIGIT。此外，Tregs 中的 BATF 缺失导致造血干细胞（HSCs）、多能祖细胞（MPPs）和粒细胞-巨噬细胞祖细胞（GMPs）数量增加，同时降低髓系祖细胞的功能和共同淋巴祖细胞的生成。此外，缺乏 BATF 的 Tregs 无法支持 BM 中 B 细胞的发育。在机制上，BATF 介导了 IL-7 信号，以促进 BM Tregs 上效应分子的表达及其稳态。我们的研究揭示了 BATF 在维持 BM Treg 稳态和功能以确保造血中的先前未被认识的作用。
