IRF-4-binding protein inhibits interleukin-17 and interleukin-21 production by controlling the activity of IRF-4 transcription factor. Academic Article uri icon

Overview

abstract

  • The T helper 17 (Th17) cell lineage is important in inflammatory and autoimmune responses, via its ability to produce interleukin-17 (IL-17) and IL-21. Given the potentially deleterious effects of Th17 cells, their generation needs to be strictly controlled. IRF-4 is a transcription factor that has recently emerged as a key regulator of Th17 cell differentiation. Here, we showed that mice deficient in a previously isolated protein, IBP (IRF-4-binding protein), rapidly developed rheumatoid arthritis-like joint disease and large-vessel vasculitis. The pathology was associated with an enhanced responsiveness of T cells to low levels of stimulation and with the inappropriate synthesis of IL-17 and IL-21. IBP sequestered IRF-4 and prevented it from targeting the transcriptional regulatory regions of the genes that encode IL-17 and IL-21. Thus, IBP appears to be important in preventing T cell-mediated autoimmunity by ensuring that the production of IL-17 and IL-21 does not occur in response to self-antigens.

publication date

  • December 8, 2008

Research

keywords

  • Arthritis, Rheumatoid
  • DNA-Binding Proteins
  • Interferon Regulatory Factors
  • Interleukin-17
  • Interleukins
  • Nuclear Proteins
  • Vasculitis

Identity

PubMed Central ID

  • PMC2633410

Scopus Document Identifier

  • 57449105853

Digital Object Identifier (DOI)

  • 10.1016/j.immuni.2008.10.011

PubMed ID

  • 19062315

Additional Document Info

volume

  • 29

issue

  • 6