The transcription factor Twist1 limits T helper 17 and T follicular helper cell development by repressing the gene encoding the interleukin-6 receptor α chain.
Cytokine responsiveness is a critical component of the ability of cells to respond to the extracellular milieu. Transcription factor-mediated regulation of cytokine receptor expression is a common mode of altering responses to the external environment. We identify the transcription factor Twist1 as a component of a STAT3-induced feedback loop that controls IL-6 signals by directly repressing Il6ra. Human and mouse T cells lacking Twist1 have an increased ability to differentiate into Th17 cells. Mice with a T cell-specific deletion of Twist1 demonstrate increased Th17 and T follicular helper cell development, early onset experimental autoimmune encephalomyelitis, and increased antigen-specific antibody responses. Thus, Twist1 has a critical role in limiting both cell-mediated and humoral immunity.
Department of Pediatrics, Herman B. Wells Center for Pediatric Research; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Duy
D
Pham
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Crystal C
CC
Walline
Department of Pediatrics, Herman B. Wells Center for Pediatric Research.
Kristin
K
Hollister
Department of Pediatrics, Herman B. Wells Center for Pediatric Research.
Alexander L
AL
Dent
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202.
Janice S
JS
Blum
Department of Pediatrics, Herman B. Wells Center for Pediatric Research.
Anthony B
AB
Firulli
Department of Pediatrics, Herman B. Wells Center for Pediatric Research; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana 46202. Electronic address: mkaplan2@iupui.edu.
Mark H
MH
Kaplan
D000818:Animals; D000917:Antibody Formation / Q000502:physiology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology*; D056724:Immunity, Humoral / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology*; D019947:Receptors, Interleukin-6 / Q000235:genetics / Q000276:immunology*; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology*; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000276:immunology*
C508603:IL6R protein, human; D009687:Nuclear Proteins; D019947:Receptors, Interleukin-6; D012097:Repressor Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse
Autoimmunity; Differentiation; Inflammation; Interleukin; STAT Transcription Factor; STAT3; T Cell Biology; T Helper Cell; Transcription Factors