Abstract
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.
MeSH terms
-
Animals
-
Bronchoalveolar Lavage Fluid / chemistry
-
Bronchoalveolar Lavage Fluid / immunology
-
Cells, Cultured
-
DNA-Binding Proteins / genetics
-
DNA-Binding Proteins / immunology*
-
DNA-Binding Proteins / metabolism
-
Flow Cytometry
-
GATA3 Transcription Factor / genetics
-
GATA3 Transcription Factor / immunology
-
GATA3 Transcription Factor / metabolism
-
Green Fluorescent Proteins / genetics
-
Green Fluorescent Proteins / metabolism
-
Immunity, Innate / immunology*
-
Interleukin-1 Receptor-Like 1 Protein
-
Interleukin-13 / genetics
-
Interleukin-13 / immunology
-
Interleukin-13 / metabolism
-
Interleukin-17 / genetics
-
Interleukin-17 / immunology
-
Interleukin-17 / metabolism
-
Interleukin-33
-
Interleukins / pharmacology
-
Lung / immunology
-
Lung / metabolism
-
Lymphocyte Activation / drug effects
-
Lymphocyte Activation / immunology
-
Mice
-
Mice, Inbred Strains
-
Mice, Knockout
-
Mice, Transgenic
-
Nippostrongylus / immunology
-
Nippostrongylus / physiology
-
Oligonucleotide Array Sequence Analysis
-
Receptors, Interleukin / genetics
-
Receptors, Interleukin / immunology
-
Receptors, Interleukin / metabolism
-
Reverse Transcriptase Polymerase Chain Reaction
-
Strongylida Infections / immunology
-
Strongylida Infections / parasitology
-
Th2 Cells / immunology*
-
Th2 Cells / metabolism
-
Th2 Cells / parasitology
-
Transcription Factors / genetics
-
Transcription Factors / immunology*
-
Transcription Factors / metabolism
-
Transcriptome / genetics
-
Transcriptome / immunology*
Substances
-
DNA-Binding Proteins
-
GATA3 Transcription Factor
-
Gata3 protein, mouse
-
Gfi1 protein, mouse
-
Il1rl1 protein, mouse
-
Il33 protein, mouse
-
Interleukin-1 Receptor-Like 1 Protein
-
Interleukin-13
-
Interleukin-17
-
Interleukin-33
-
Interleukins
-
Receptors, Interleukin
-
Transcription Factors
-
Green Fluorescent Proteins
Associated data
-
GEO/GSE45621
-
GEO/GSE50806