Article

TGFbeta and retinoic acid intersect in immune-regulation.

La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Cell adhesion & migration (impact factor: 1.82). 08/2007; 1(3):142-4. pp.142-4
Source: PubMed

ABSTRACT Transforming growth factor (TGFbeta) prevents T(H)1 and T(H)2 differentiation and converts naïve CD4 cells into Foxp3-expressing T regulatory (Treg) cell.(1,2) In sharp contrast, in the presence of pro-inflammatory cytokines, including IL-6, TGFbeta not only inhibits Foxp3 expression but also promotes the differentiation of pro-inflammatory IL17-producing CD4 effector T (T(H)17) cells.(3-5) This reciprocal TGFbeta-dependent differentiation imposes a critical dilemma between pro- and anti-inflammatory immunity and suggests that a sensitive regulatory mechanism must exist to control TGFbeta-driven T(H)17 effector and Treg differentiation. A vitamin A metabolite, retinoic acid (RA), was recently identified as a key modulator of TGFbeta-driven- immune deviation capable of suppressing T(H)17 differentiation while promoting Foxp3(+)Treg generation.(6-10).

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  • Article: Runx3 regulates dendritic epidermal T cell development.
    Eilon Woolf, Ori Brenner, Dalia Goldenberg, Ditsa Levanon, Yoram Groner
    [show abstract] [hide abstract]
    ABSTRACT: The Runx3 transcription factor regulates development of T cells during thymopoiesis and TrkC sensory neurons during dorsal root ganglia neurogenesis. It also mediates transforming growth factor-beta signaling in dendritic cells and is essential for development of skin Langerhans cells. Here, we report that Runx3 is involved in the development of skin dendritic epidermal T cells (DETCs); an important component of tissue immunoregulation. In developing DETCs, Runx3 regulates expression of the alphaEbeta7 integrin CD103, known to affect migration and epithelial retention of DETCs. It also regulates expression of IL-2 receptor beta (IL-2Rbeta) that mediates cell proliferation in response to IL-2 or IL-15. In the absence of Runx3, the reduction in CD103 and IL-2Rbeta expression on Runx3(-/-) DETC precursors resulted in impaired cell proliferation and maturation, leading to complete lack of skin DETCs in Runx3(-/-) mice. The data demonstrate the requirement of Runx3 for DETCs development and underscore the importance of CD103 and IL-2Rbeta in this process. Of note, while Runx3(-/-) mice lack both DETCs and Langerhans cells, the two most important components of skin immune surveillance, the mice did not develop skin lesions under pathogen-free (SPF) conditions.
    Developmental Biology 04/2007; 303(2):703-14. · 4.07 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

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Keywords

anti-inflammatory immunity
 
control TGFbeta-driven T(H)17 effector
 
converts naïve CD4 cells
 
critical dilemma
 
Foxp3(+)Treg generation
 
Foxp3-expressing T regulatory
 
key modulator
 
reciprocal TGFbeta-dependent differentiation
 
sensitive regulatory mechanism
 
sharp contrast
 
suppressing T(H)17 differentiation
 
T(H)2 differentiation
 
TGFbeta-driven- immune deviation capable
 
Treg differentiation