The signaling adapter p62 is an important mediator of T helper 2 cell function and allergic airway inflammation.
Naïve T helper (Th) cells differentiate in response to antigen stimulation into either Th1 or Th2 effector cells, which are characterized by the secretion of different set of cytokines. Th2 differentiation, which is critical for allergic airway disease, is triggered by signals of the T-cell receptor (TCR) and the cytokines generated during polarization, particularly IL-4. We determine here the potential role of the signaling adapter p62 in T-cell polarization. We report using p62-/- mice and cells that p62 acts downstream TCR activation, and is important for Th2 polarization and asthma, playing a significant role in the control of the sustained activation of NF-kappaB and late synthesis of GATA3 and IL-4 by participating in the activation of the IKK complex.
Martin
Pilar
P
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Cantoblanco, Madrid, Spain.
Diaz-Meco
Maria T
MT
Moscat
Jorge
J
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D019169:Jurkat Cells; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000071456:Sequestosome-1 Protein; D015398:Signal Transduction; D018418:Th2 Cells / Q000276:immunology*
D048868:Adaptor Proteins, Signal Transducing; D050990:GATA3 Transcription Factor; D006360:Heat-Shock Proteins; D016328:NF-kappa B; D011948:Receptors, Antigen, T-Cell; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D015847:Interleukin-4