title: Interleukin-5-producing group 2 innate lymphoid cells control eosinophilia induced by interleukin-2 therapy.
abstract: Interleukin (IL)-2 promotes regulatory T-cell development and function, and treatment with IL-2 is being tested as therapy for some autoimmune diseases. However, patients receiving IL-2 treatment also experience eosinophilia due to an unknown mechanism. Here, we show that patients receiving low-dose IL-2 have elevated levels of serum IL-5, and this correlates with their degree of eosinophilia. In mice, low-dose IL-2-anti-IL-2 antibody complexes drove group 2 innate lymphoid cells (ILC2) to produce IL-5 and proliferate. Using genetic approaches in mice, we demonstrate that activation of ILC2 was responsible for the eosinophilia observed with IL-2 therapy. These observations reveal a novel cellular network that is activated during IL-2 treatment. A better understanding of the cross talk between these cell populations may lead to more effective targeting of IL-2 to treat autoimmune disease.
authors.affiliation: Diabetes Center.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Van Gool
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, and Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA;
authors.forename: Ari B
authors.initials: AB
authors.lastname: Molofsky
authors.affiliation: Diabetes Center.
authors.forename: Malika M
authors.initials: MM
authors.lastname: Morar
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (I2B), Paris, France; and.
authors.forename: Michelle
authors.initials: M
authors.lastname: Rosenzwajg
authors.affiliation: Howard Hughes Medical Institute and.
authors.forename: Hong-Erh
authors.initials: HE
authors.lastname: Liang
authors.affiliation: Assistance Publique - Hôpitaux de Paris, Hôpital Pitié-Salpêtrière, Biotherapy (CIC-BTi) and Inflammation-Immunopathology-Biotherapy Department (I2B), Paris, France; and.
authors.forename: David
authors.initials: D
authors.lastname: Klatzmann
authors.affiliation: Department of Microbiology, Immunology, and Molecular Genetics, and Howard Hughes Medical Institute and Department of Medicine, University of California, San Francisco, San Francisco, CA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Locksley
authors.affiliation: Diabetes Center, Department of Microbiology, Immunology, and Molecular Genetics, and.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D004802:Eosinophilia / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000276:immunology / Q000494:pharmacology*; D015848:Interleukin-5 / Q000276:immunology*; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice
chemical_list: D000906:Antibodies; D007376:Interleukin-2; D015848:Interleukin-5