CD45 alleviates airway inflammation and lung fibrosis by limiting expansion and activation of ILC2s

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 120; no. 36; p. e2215941120
• Main Authors: Cui, Guangwei, Shimba, Akihiro, Jin, Jianshi, Hojo, Nozomi, Asahi, Takuma, Abe, Shinya, Ejima, Aki, Okada, Shinri, Ohira, Keizo, Kato, Ryoma, Tani-ichi, Shizue, Yamada, Ryo, Ebihara, Takashi, Shiroguchi, Katsuyuki, Ikuta, Koichi
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.09.2023
• Subjects: Allergies; Animals; Biological Sciences; Bone marrow; CD45 antigen; Constraining; Fibrosis; Galectin-9; Glycolysis; Homeostasis; Immune response; Immunity, Innate; Inflammation; Inflammatory diseases; Inflammatory response; Lung diseases; Lungs; Lymphocytes; Lymphocytes T; Lymphoid cells; Mice; Parasites; Pathogenesis; Phenotypes; Population number; Protein-tyrosine-phosphatase; Pulmonary Fibrosis - prevention & control; Respiratory tract diseases; Signal Transduction; Tyrosine; airway inflammation; innate lymphoid cell; fibrosis; metabolism; CD45
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.2215941120

Group 2 innate lymphoid cells (ILC2s) are critical for the immune response against parasite infection and tissue homeostasis and involved in the pathogenesis of allergy and inflammatory diseases. Although multiple molecules positively regulating ILC2 development and activation have been extensively investigated, the factors limiting their population size and response remain poorly studied. Here, we found that CD45, a membrane-bound tyrosine phosphatase essential for T cell development, negatively regulated ILC2s in a cell-intrinsic manner. ILC2s in CD45-deficient mice exhibited enhanced proliferation and maturation in the bone marrow and hyperactivated phenotypes in the lung with high glycolytic capacity. Furthermore, CD45 signaling suppressed the type 2 inflammatory response by lung ILC2s and alleviated airway inflammation and pulmonary fibrosis. Finally, the interaction with galectin-9 influenced CD45 signaling in ILC2s. These results demonstrate that CD45 is a cell-intrinsic negative regulator of ILC2s and prevents lung inflammation and fibrosis via ILC2s.