BMP Signaling Alleviates Allergic Airway Inflammation by Controlling Group 2 Innate Lymphoid Cells Homeostasis

Recent studies have highlighted the important role of bone morphogenetic proteins (BMPs) in immunoregulation. Our earlier work identified the expression of BMP receptors on lymphoid progenitors and group 2 innate lymphoid cells (ILC2s) in the bone marrow. However, the precise function of BMP signaling in the development and activity of ILC2s remains unclear. This study aimed to investigate whether BMP signaling regulates the generation of ILC2s and their effector functions during lung airway inflammation. We generated BMP receptor 2 (BMPR2) conditional knockout (CKO) mice to analyze ILC2 development and function. We found that BMPR2 deficiency led to an increased number of ILC2s in the lung at steady state, primarily due to enhanced cell proliferation. This expansion resulted in aggravation of early type 2 response in a papain-induced allergic airway inflammation model. BMP4 restrained the proliferation of ILC2s in vitro and in vivo through activation of the canonical BMP signaling pathway. Administration of BMP4 alleviated papain-induced airway inflammation in control mice, whereas this therapeutic effect was abolished in BMPR2 conditional knockout mice. In conclusion, our study demonstrated that BMP signaling regulates allergic airway inflammation by controlling ILC2s homeostasis.