Th9 cells: differentiation and disease

Abstract

Summary CD4+ T-helper cells regulate immunity and inflammation through the acquisition of potential to secrete specific cytokines. The acquisition of cytokine-secreting potential, in a process termed T-helper cell differentiation, is a response to multiple environmental signals including the cytokine milieu. The most recently defined subset of T-helper cells are termed Th9 and are identified by the potent production of interleukin-9 (IL-9). Given the pleiotropic functions of IL-9, Th9 cells might be involved in pathogen immunity and immune-mediated disease. In this review, I focus on recent developments in understanding the signals that promote Th9 differentiation, the transcription factors that regulate IL-9 expression, and finally the potential roles for Th9 cells in immunity in vivo.

Potential involvement of IL-9 and Th9 cells in the pathogenesis of rheumatoid arthritis

“…Although initially characterized as Th2 cell derived, a new IL-9-producing Th cell subset, namely Th9 cells, has been demonstrated [2]. Th9 effector cells are distinct from Th2 cells and can be differentiated in vitro via TCR stimulation in the presence of TGF-b and IL-4, or directly in the presence of TSLP [2,4].…”

“…Th9 effector cells are distinct from Th2 cells and can be differentiated in vitro via TCR stimulation in the presence of TGF-b and IL-4, or directly in the presence of TSLP [2,4]. Given the pleiotropic functions of IL-9, Th9 cells might be involved in several types of inflammatory disease.…”

“…3DI). Since Th9 polarization has been demonstrated to be dependent on IL-4, TGF-b and TSLP [2,4], we next evaluated their expression in synovial tissues from patients and controls. A significant upregulation of IL-4 ( Fig.…”

“…In addition to Th1, Th17 and Th2 cells, another subset of effector T cells, identified by the production of IL-9 and named Th9 cells, with a potential role in T-cell-dependent B-cell differentiation, expansion and antibody production, has also been described [2,3]. The development of Th9 cells requires a balance of signals from cytokines such as IL-4 and TGF-b [2], and from epithelial cytokines such as thymic stromal lymphopoietin (TSLP) [4].…”

Tumor-specific IL-9–producing CD8+Tc9 cells are superior effector than type-I cytotoxic Tc1 cells for adoptive immunotherapy of cancers

“…1B). However, the expression of Irf4 and Pu.1, two transcription factors governing Th9-cell lineage development (19), was significantly up-regulated in Tc9 cells (Fig. 1B).…”