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Th17 cells in Behçet's disease: a new immunoregulatory axis

Department of Basic Sciences, Medicine School of Tunis, University Tunis El Manar, Tunisia.

CER4725 Submission on line
2011 Vol.29, N°4 ,Suppl.67 - PI 0071, PF 0076
Review

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Rheumatology Article

 

Abstract

Accumulating evidence suggests that the abnormality of innate and adaptive immunity responses plays an important role in Behçet`s disease (BD). T helper (Th) cells have a central role in modulating immune responses. Traditionally, BD is regarded as a Th1-mediated inflammatory disease. Recently, Th17 cells were identified as a new subset of Th cells unrelated to Th1 or Th2 cells, and several cytokines are involved in regulating their activation and differentiation. Naïve murine CD4+ Th can be induced to differentiate towards Th1, Th2, Th17 and Treg phenotypes according to the local cytokine milieu. The committed cells are characterised by expression of specific transcription factors, T bet for Th1, GATA-3 for Th2, Foxp3 for Tregs and RORγt (RORγt/RORC) for Th17 cells. It has been demonstrated that the skewing of murine Th towards Th17 and Treg is mutually exclusive. Th17 cells regulate inflammation via production of distinct cytokines such as interleukin (IL)-17. There is growing evidence that Th17 cells are pathological in many human autoimmune and inflammatory diseases, leading to intense interest in defining their origins, functions and developing strategies to block their pathological effects. Evidence from human disease such as BD suggests that specialised antigen-presenting cells drive their in vivo development. Knowledge of how Th17 cells interact with other immune cells is limited, but recent data suggest that Th17 cells may not be subject to strict cellular regulation by T regulatory cells. Notably, Th17 cells and Treg cells appear to share common developmental pathways and both cell types retain significant plasticity. Herein, we will discuss the molecular and cellular regulation of Th17 cells with an emphasis on BD. The identification of Th17 cells helps us to explain some of the anomalies seen in the Th1/Th2 axis and has broadened our understanding of the immunopathological effects of Th17 cells in the development of BD.

PMID: 21968241 [PubMed]

Received: 01/05/2011 - Accepted : 12/09/2011 - In Press: 27/09/2011 - Published: 27/09/2011