The transcription factor GATA3 is essential for the function of human type 2 innate lymphoid cells.
Type 2 innate lymphoid cells (ILC2s) are part of a large family of ILCs that are important effectors in innate immunity, lymphoid organogenesis, and tissue remodeling. ILC2s mediate parasite expulsion but also contribute to airway inflammation, emphasizing the functional similarity between these cells and Th2 cells. Consistent with this, we report that the transcription factor GATA3 was highly expressed by human ILC2s. CRTH2(+) ILC2s were enriched in nasal polyps of patients with chronic rhinosinusitis, a typical type 2-mediated disease. Nasal polyp epithelial cells expressed TSLP, which enhanced STAT5 activation, GATA3 expression, and type 2 cytokine production in ILC2s. Ectopic expression of GATA3 in Lin(-)CD127(+)CRTH2(-) cells resulted in induction of CRTH2 and the capacity to produce high amounts of type 2 cytokines in response to TSLP plus IL-33. Hence, we identify GATA3, potently regulated by TSLP, as an essential transcription factor for the function of human ILC2s.
Tytgat Institute for Liver and Intestinal Research, University of Amsterdam, The Netherlands.
Jenny
J
Mjösberg
Jochem
J
Bernink
Korneliusz
K
Golebski
Julien J
JJ
Karrich
Charlotte P
CP
Peters
Bianca
B
Blom
Anje A
AA
te Velde
Wytske J
WJ
Fokkens
Cornelis M
CM
van Drunen
Hergen
H
Spits
D002460:Cell Line; D016207:Cytokines / Q000276:immunology; D004848:Epithelium / Q000276:immunology; D050990:GATA3 Transcription Factor / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007113:Immunity, Innate; D018793:Interleukin-13 / Q000096:biosynthesis / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D009298:Nasal Polyps / Q000276:immunology; D018121:Receptors, Cytokine / Q000235:genetics / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin
C498762:CRLF2 protein, human; D016207:Cytokines; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D018793:Interleukin-13; D018121:Receptors, Cytokine; D050799:STAT5 Transcription Factor; D000094632:Thymic Stromal Lymphopoietin