IL-1 is a critical regulator of group 2 innate lymphoid cell function and plasticity.
Group 2 innate lymphoid cells (ILC2 cells) are important for type 2 immune responses and are activated by the epithelial cytokines interleukin 33 (IL-33), IL-25 and thymic stromal lymphopoietin (TSLP). Here we demonstrated that IL-1β was a critical activator of ILC2 cells, inducing proliferation and cytokine production and regulating the expression of epithelial cytokine receptors. IL-1β also governed ILC2 plasticity by inducing low expression of the transcription factor T-bet and the cytokine receptor chain IL-12Rβ2, which enabled the conversion of these cells into an ILC1 phenotype in response to IL-12. This transition was marked by an atypical chromatin landscape characterized by the simultaneous transcriptional accessibility of the locus encoding interferon-γ (IFN-γ) and the loci encoding IL-5 and IL-13. Finally, IL-1β potentiated ILC2 activation and plasticity in vivo, and IL-12 acted as the switch that determined an ILC2-versus-ILC1 response. Thus, we have identified a previously unknown role for IL-1β in facilitating ILC2 maturation and plasticity.
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.|R&D Research, MedImmune, Gaithersburg, Maryland, USA.
Yoichiro
Y
Ohne
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
Jonathan S
JS
Silver
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.
LuAnn
L
Thompson-Snipes
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.
Magalie A
MA
Collet
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.
Jean Philippe
JP
Blanck
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.
Brandi L
0000-0003-4126-4478
BL
Cantarel
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
Alan M
AM
Copenhaver
Department of Respiratory, Inflammation and Autoimmunity, MedImmune, Gaithersburg, Maryland, USA.
Alison A
AA
Humbles
Baylor Research Institute, Baylor Scott and White Health, Dallas, Texas, USA.|R&D Research, MedImmune, Gaithersburg, Maryland, USA.
Yong-Jun
YJ
Liu
D000818:Animals; D002454:Cell Differentiation; D000066670:Cell Plasticity / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D016513:Mice, SCID; D053707:Receptors, Interleukin-12 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D020825:T-Box Domain Proteins / Q000235:genetics / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D058408:Th1-Th2 Balance; D018418:Th2 Cells / Q000276:immunology; D000094632:Thymic Stromal Lymphopoietin; D000098815:T-bet Transcription Factor
D016207:Cytokines; C508439:IL12RB2 protein, human; C486701:IL25 protein, human; C506536:IL33 protein, human; D020381:Interleukin-17; D053583:Interleukin-1beta; D000067596:Interleukin-33; D053707:Receptors, Interleukin-12; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D018664:Interleukin-12; D007371:Interferon-gamma; D000094632:Thymic Stromal Lymphopoietin