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Foxo transcription factors control regulatory T cell development and function. | LitMetric

Foxo transcription factors control regulatory T cell development and function.

Immunity

Molecular Biology Section, Division of Biological Sciences and Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093-0377, USA.

Published: December 2010

AI Article Synopsis

  • Foxo transcription factors are crucial for regulating various immune cell functions, particularly in T cell development and survival.
  • The study found that lacking Foxo1 significantly impaired the development and functionality of regulatory T cells, leading to severe immune-related issues.
  • Additionally, the absence of Foxo1 disrupted normal T cell responses and worsened effects when Foxo3 was also missing, highlighting their key role in T cell differentiation and function.

Article Abstract

Foxo transcription factors integrate extrinsic signals to regulate cell division, differentiation and survival, and specific functions of lymphoid and myeloid cells. Here, we showed the absence of Foxo1 severely curtailed the development of Foxp3(+) regulatory T (Treg) cells and those that developed were nonfunctional in vivo. The loss of function included diminished CTLA-4 receptor expression as the Ctla4 gene was a direct target of Foxo1. T cell-specific loss of Foxo1 resulted in exocrine pancreatitis, hind limb paralysis, multiorgan lymphocyte infiltration, anti-nuclear antibodies and expanded germinal centers. Foxo-mediated control over Treg cell specification was further revealed by the inability of TGF-β cytokine to suppress T-bet transcription factor in the absence of Foxo1, resulting in IFN-γ secretion. In addition, the absence of Foxo3 exacerbated the effects of the loss of Foxo1. Thus, Foxo transcription factors guide the contingencies of T cell differentiation and the specific functions of effector cell populations.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3034255PMC
http://dx.doi.org/10.1016/j.immuni.2010.12.002DOI Listing

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