The IL-33 receptor (ST2) regulates early IL-13 production in fungus-induced allergic airway inflammation
| Autor: | Bianca Schulze, Uwe Müller, Andreas Grahnert, Martina Protschka, Daniel Piehler, Gottfried Alber, Maria Eschke, Tina Richter, Laura Heyen, Gabriele Köhler, Frank Brombacher |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Antigens Fungal medicine.medical_treatment Immunology Mice Transgenic GATA3 Transcription Factor Biology Lymphocyte Activation 03 medical and health sciences Mice 0302 clinical medicine Th2 Cells Antigen Immunity medicine Hypersensitivity Immunology and Allergy Animals Lymphocytes Cells Cultured Cell Proliferation Mice Knockout Interleukin-13 Innate lymphoid cell FOXP3 Cryptococcosis Receptors Interleukin Allergens Macrophage Activation Acquired immune system Interleukin-1 Receptor-Like 1 Protein Immunity Innate Interleukin 33 030104 developmental biology Cytokine Interleukin 13 Cryptococcus neoformans Female 030215 immunology |
| Zdroj: | Mucosal immunology. 9(4) |
| ISSN: | 1935-3456 |
| Popis: | Allergic airway inflammation (AAI) in response to environmental antigens is an increasing medical problem, especially in the Western world. Type 2 interleukins (IL) are central in the pathological response but their importance and cellular source(s) often rely on the particular allergen. Here, we highlight the cellular sources and regulation of the prototypic type 2 cytokine, IL-13, during the establishment of AAI in a fungal infection model using Cryptococcus neoformans. IL-13 reporter mice revealed a rapid onset of IL-13 competence within innate lymphoid cells type 2 (ILC2) and IL-33R(+) T helper (Th) cells. ILC2 showed IL-33-dependent proliferation upon infection and significant IL-13 production. Th cells essentially required IL-33 to become either GATA3(+) or GATA3(+)/Foxp3(+) hybrids. GATA3(+) Th cells almost exclusively contributed to IL-13 production but hybrid GATA3(+)/Foxp3(+) Th cells did not. In addition, alveolar macrophages upregulated the IL-33R and subsequently acquired a phenotype of alternative activation (Ym1(+), FIZZ1(+), and arginase-1(+)) linked to type 2 immunity. Absence of adaptive immunity in rag2(-/-) mice resulted in attenuated AAI, revealing the need for Th2 cells for full AAI development. Taken together, in pulmonary cryptococcosis ILC2 and GATA3(+) Th2 cells produce early IL-13 largely IL-33R-dependent, thereby promoting goblet cell metaplasia, pulmonary eosinophilia, and alternative activation of alveolar macrophages. |
| Databáze: | OpenAIRE |
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