Specification of type 2 innate lymphocytes by the transcriptional determinant Gfi1
| Autor: | Jason DeVoss, Jeffrey Eastham-Anderson, Donghong Yan, Justin Lesch, Aly A. Khan, Harinder Singh, Lauri Diehl, Vladimir Ramirez-Carrozzi, Robert Soriano, Meijuan Zhou, Wyne P. Lee, Rajita Pappu, Chauncey J. Spooner, Zora Modrusan, Min Xu, Alexander R. Abbas |
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| Rok vydání: | 2013 |
| Předmět: |
Immunology
Green Fluorescent Proteins Interleukin-1 Receptor-Like 1 Protein Inflammation Mice Inbred Strains Mice Transgenic GATA3 Transcription Factor Biology Lymphocyte Activation Allergic inflammation Mice Immune system Th2 Cells Immunity medicine Immunology and Allergy Animals Lung Cells Cultured Oligonucleotide Array Sequence Analysis Strongylida Infections Mice Knockout Interleukin-13 Effector Reverse Transcriptase Polymerase Chain Reaction Interleukins Innate lymphoid cell Interleukin-17 Receptors Interleukin Flow Cytometry Interleukin-33 Immunity Innate Interleukin 33 DNA-Binding Proteins Nippostrongylus medicine.symptom Transcriptome Bronchoalveolar Lavage Fluid Transcription Factors |
| Zdroj: | Nature immunology. 14(12) |
| ISSN: | 1529-2916 |
| Popis: | Type 2 innate lymphoid cells (ILC2 cells) participate in host defense against helminth parasites and in allergic inflammation. Given their functional relatedness to type 2 helper T cells (T(H)2 cells), we explored whether Gfi1 acts as a shared transcriptional determinant in ILC2 cells. Gfi1 promoted the development of ILC2 cells and controlled their responsiveness during infection with Nippostrongylus brasiliensis and protease allergen-induced lung inflammation. Gfi1 'preferentially' regulated the responsiveness of ILC2 cells to interleukin 33 (IL-33) by directly activating Il1rl1, which encodes the IL-33 receptor (ST2). Loss of Gfi1 in activated ILC2 cells resulted in impaired expression of the transcription factor GATA-3 and a dysregulated genome-wide effector state characterized by coexpression of IL-13 and IL-17. Our findings establish Gfi1 as a shared determinant that reciprocally regulates the type 2 and IL-17 effector states in cells of the innate and adaptive immune systems. |
| Databáze: | OpenAIRE |
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