Involvement of Yin Yang 1 (YY1) Expression in T-Cell Subsets Differentiation and Their Functions: Implications in T Cell-Mediated Diseases.

Abstract

The transcription factor Yin Yang 1 (YY1) has been implicated in embryogenesis, cell differentiation, organ development, and regulation of T cell-mediated immune diseases. YY1 has been reported to act as an activator or repressor, or both, of various genes depending on the nature of the tissue and their context. Although the roles of YY1 in both pathogenesis and progression of tumors has been the subject of many reports, the roles of YY1 in the immune system are not as well known. In this review, we examine the literature on the role of YY1 in both the differentiation and the development of various subsets of the T lymphocytes and examined its molecular role in these areas. We examined the role of YY1 in the thymus for the development of both CD4 and CD8 T lymphocytes, the various CD4 subsets, Th1, Th2, Th17, and Treg. Our analyses revealed that the presence of YY1 is necessary for maturation and proliferation of the αβ lineage through its role in mediating the apoptotic pathway. Moreover, in differentiation of T cell subsets, YY1 controls the expression of the Th2 master regulator GATA3, the Treg inducer Foxp3, as well as IL-12 expression, which is important in regulating production of Th1 cytokines. Furthermore, the role of YY1 in the Th17 signaling pathway has not been fully identified, although recent studies have suggested that differentiation of Th17 involves synergistic action of YY1 and STAT3. The previously mentioned findings strongly suggest that the role of YY1 in T cells is critical in both their normal differentiation and the induction of T cell-mediated autoimmune diseases. Clearly, such findings suggest the potential therapeutic applications of YY1 inhibitors to alleviate its role in autoimmune diseases.