T-cell effector pathways in allergic diseases: Transcriptional mechanisms and therapeutic targets - 15/08/11
, Ning Li, PhD b, Maria Garcia-Lloret, MD a, Hyon-Jeen Kim, PhD b, Andre E. Nel, MD, PhD b, ⁎ 
Reprint requests: Andre E. Nel, MD, PhD, or Talal A. Chatila, MD, David Geffen School of Medicine, University of California at Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1752.Abstract |
Originally interpreted within the framework of a binary TH1/TH2 paradigm, our knowledge of the pathogenesis of atopic diseases has broadened to incorporate the contribution of T regulatory cells and the newly described proinflammatory TH17 cell lineage. The commitment of peripheral T-cell clones to undergo differentiation into one of those lineages is shaped by self-reinforcing transcriptional circuitries that center on key transcriptional regulators: T-box expressed in T cells (TH1), GATA-3 (TH2), forkhead box p3 (T regulatory cells), and retinoid-related orphan receptor γτ/retinoid-related orphan receptor ⍺ (TH17). These circuits function both to establish the respective lineage phenotype and to enable epigenetic changes that maintain those phenotypes long-term. This evolving view of how signaling and transcriptional networks generate effector T-cell responses suggests novel therapeutic approaches to reprogram effector T-cell lineage commitment in allergic diseases in favor of tolerance induction.
Le texte complet de cet article est disponible en PDF.Key words : Transcriptional regulation, T-cell differentiation, TH1, TH2, Treg, TH17, T-bet, GATA-3, Foxp3, RORγτ, atopic disease, asthma, therapeutic strategies, oxidative stress, Nrf2
Abbreviations used : ARE, aTreg, c-MAF, Foxp3, GR, IL-12Rβ1, IPEX, NFAT, NR, Nrf2, nTreg, ROR, RUNX, STAT, T-bet, TCR, TF, Tr-1, Treg
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| (Supported by an educational grant from Merck & Co., Inc.) |
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| Series editors: Joshua A. Boyce, MD, Fred Finkelman, MD, William T. Shearer, MD, PhD, and Donata Vercelli, MD |
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| Supported by the National Institute of Allergy and Infectious Diseases–funded University of California at Los Angeles Asthma and Allergic Disease Clinical Research Center (U19 AI070453), a US Environmental Protection Agency (Science to Achieve Results) grant to the Southern California Particle Center, and National Institutes of Health grant 2R01AI065617 (T.A.C.). |
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| Disclosure of potential conflict of interest: A. E. Nel has served as an expert witness in alleged rate effects of vaccine components and mold litigation. The rest of the authors have declared that they have no conflict of interest. |
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| Terms in boldface and italics are defined in the glossary on page 813. |
Vol 121 - N° 4
P. 812-823 - avril 2008 Retour au numéro
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- Therapeutic approaches for control of transcription factors in allergic disease
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