Differential Expression of Interleukin-17A and -17F Is Coupled to T Cell Receptor Signaling via Inducible T Cell Kinase

Julio Gomez-Rodriguez, Nisebita Sahu, Robin Handon, Todd S. Davidson, Stacie M. Anderson, Martha R. Kirby, Avery August, Pamela L. Schwartzberg

Research output: Contribution to journalArticle

129 Scopus citations

Abstract

T helper 17 (Th17) cells play major roles in autoimmunity and bacterial infections, yet how T cell receptor (TCR) signaling affects Th17 cell differentiation is relatively unknown. We demonstrate that CD4+ T cells lacking Itk, a tyrosine kinase required for full TCR-induced phospholipase C-γ (PLC-γ1) activation, exhibit decreased interleukin-17A (IL-17A) expression in vitro and in vivo, despite relatively normal expression of retinoic acid receptor-related orphan receptor-γT (ROR-γT) and IL-17F. IL-17A expression was rescued by pharmacologically induced Ca2+ influx or constitutively activated nuclear factor of activated T cells (NFAT). Conversely, decreased TCR stimulation or calcineurin inhibition preferentially reduced IL-17A expression. We further found that the promoter of Il17a but not Il17f has a conserved NFAT binding site that bound NFATc1 in wild-type but not Itk-deficient cells, even though both exhibited open chromatin conformations. Finally, Itk-/- mice also showed differential regulation of IL-17A and IL-17F in vivo. Our results suggest that Itk specifically couples TCR signaling to Il17a expression and the differential regulation of Th17 cell cytokines through NFATc1.

Original languageEnglish (US)
Pages (from-to)587-597
Number of pages11
JournalImmunity
Volume31
Issue number4
DOIs
StatePublished - Oct 16 2009

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Differential Expression of Interleukin-17A and -17F Is Coupled to T Cell Receptor Signaling via Inducible T Cell Kinase'. Together they form a unique fingerprint.

  • Cite this

    Gomez-Rodriguez, J., Sahu, N., Handon, R., Davidson, T. S., Anderson, S. M., Kirby, M. R., August, A., & Schwartzberg, P. L. (2009). Differential Expression of Interleukin-17A and -17F Is Coupled to T Cell Receptor Signaling via Inducible T Cell Kinase. Immunity, 31(4), 587-597. https://doi.org/10.1016/j.immuni.2009.07.009