Th9 cells, new players in adaptive immunity

Trends Immunol. 2014 Feb;35(2):61-8. doi: 10.1016/ Epub 2013 Nov 8.


Upon antigen-specific stimulation, naïve CD4⁺ T cells have the potential to differentiate into various T helper (Th) cell subsets. Earlier models of Th cell differentiation focused on IFN-γ-producing Th1 cells and IL-4-secreting Th2 cells. The discovery of additional CD4⁺ Th cell subsets has extended our understanding of Th cell differentiation beyond this dichotomy. Among these is the recently described Th9 cell subset, which preferentially produces interleukin (IL)-9. Here, we review the latest developments in Th9 cell development and differentiation, focusing on contributing environmental signals, and discuss potential physiological and pathophysiological functions of these cells. We describe the challenges inherent to unambiguously defining roles for Th9 cells using the available experimental animal models, and suggest new experimental models to address these concerns.

Keywords: T helper cell; Th9; cytokine; interleukin-9; lymphocyte differentiation; plasticity; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adaptive Immunity
  • Animals
  • Humans
  • Hypersensitivity / immunology
  • Interferon Regulatory Factors / genetics
  • Interferon Regulatory Factors / metabolism
  • Interleukin-9 / biosynthesis*
  • Interleukin-9 / genetics
  • Mice
  • Models, Immunological
  • Neoplasms / immunology
  • Receptors, Antigen, T-Cell / metabolism
  • Receptors, Interleukin-2 / metabolism
  • Receptors, Interleukin-4 / metabolism
  • Signal Transduction / immunology
  • T-Lymphocyte Subsets / classification
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocytes, Helper-Inducer / classification
  • T-Lymphocytes, Helper-Inducer / immunology*
  • Transforming Growth Factor beta / metabolism


  • Interferon Regulatory Factors
  • Interleukin-9
  • Receptors, Antigen, T-Cell
  • Receptors, Interleukin-2
  • Receptors, Interleukin-4
  • Transforming Growth Factor beta
  • interferon regulatory factor-4