%0 Journal Article
%T Skewed Helper T-Cell Responses to IL-12 Family Cytokines Produced by Antigen-Presenting Cells and the Genetic Background in Behcet¡¯s Disease
%A Jun Shimizu
%A Fumio Kaneko
%A Noboru Suzuki
%J Genetics Research International
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/363859
%X Behcet¡¯s disease (BD) is a multisystemic inflammatory disease and is characterized by recurrent attacks on eyes, brain, skin, and gut. There is evidence that skewed T-cell responses contributed to its pathophysiology in patients with BD. Recently, we found that Th17 cells, a new helper T (Th) cell subset, were increased in patients with BD, and both Th type 1 (Th1) and Th17 cell differentiation signaling pathways were overactivated. Several researches revealed that genetic polymorphisms in Th1/Th17 cell differentiation signaling pathways were associated with the onset of BD. Here, we summarize current findings on the Th cell subsets, their contribution to the pathogenesis of BD and the genetic backgrounds, especially in view of IL-12 family cytokine production and pattern recognition receptors of macrophages/monocytes. 1. Introduction Behcet¡¯s disease (BD) is a systemic inflammatory disease, characterized by recurrent signs and symptoms of oral aphthosis, genital ulcers, skin lesions, and uveitis. BD is not chronic inflammatory disease, but patients with BD suffer from recurrent attacks of acute and self-limiting inflammation. Repeated attacks of uveitis can lead to blindness. The etiology of BD is largely unknown and skewed T-cell responses are associated with the development and maintenance of BD [1]. Excessive cytokine production by Th1 cells was reported using immunohistochemistry [2, 3] and intracellular cytokine staining [4, 5]. Th1 dominance was observed in BD uveitis [6] and stomatitis as well [7]. We reported excessive Th1 cell infiltration in BD skin and intestinal lesions but interleukin- (IL-) producing T cells were rarely detected [8¨C10]. T cells and peripheral blood mononuclear cells (PBMC) from patients with BD responded to KTH1 antigens of Streptococcus sanguinis in oral cavity of patients with BD and produced interferon ¦Ã (IFN¦Ã) and IL-12 [11]. Recently, Th1/Th2 paradigm was challenged by the discovery of various subsets of Th cells, such as Th17 cells and regulatory T (Treg) cells [12] (Figure 1). Researchers showed that Th cell differentiation in each subset was closely related and sometimes converted into another subset in response to environmental signals both in peripheral blood and in organs [13]. Recent studies on innate immune system suggested that antigen-presenting cells (APC) stimulated with pattern-recognition receptors (PRR) and corresponding ligands regulated Th cell differentiation by cytokine production [14]. Figure 1: Current view of helper T (Th) cell subsets in humans [ 12]. Na£¿ve Th cells differentiate into several
%U http://www.hindawi.com/journals/gri/2013/363859/