T-cell immune adaptor SKAP1 regulates the induction of collagen-induced arthritis in mice

Immunol Lett. 2016 Aug:176:122-7. doi: 10.1016/j.imlet.2016.04.007. Epub 2016 May 12.

Abstract

SKAP1 is an immune cell adaptor that couples the T-cell receptor with the 'inside-out' signalling pathway for LFA-1 mediated adhesion in T-cells. A connection of SKAP1 to the regulation of an autoimmune disorder has not previously been reported. In this study, we show that Skap1-deficient (skap1-/-) mice are highly resistant to the induction of collagen-induced arthritis (CIA), both in terms of incidence or severity. Skap1-/- T-cells were characterised by a selective reduction in the presence IL-17+ (Th17) in response to CII peptide and a marked reduction of joint infiltrating T-cells in Skap1-/- mice. SKAP1 therefore represents a novel connection to Th17 producing T-cells and is new potential target in the therapeutic intervention in autoimmune and inflammatory diseases.

Keywords: Adaptor; Murine autoimmune arthritis; SKAP-55; SKAP1; T-cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Cell Movement
  • Collagen Type II / immunology
  • Disease Susceptibility
  • Interleukin-17 / metabolism
  • Joints / immunology*
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / metabolism
  • Mice
  • Mice, Inbred DBA
  • Mice, Knockout
  • Phosphoproteins / genetics*
  • Phosphoproteins / metabolism
  • Signal Transduction
  • Th17 Cells / immunology*

Substances

  • Collagen Type II
  • Interleukin-17
  • Lymphocyte Function-Associated Antigen-1
  • Phosphoproteins
  • SKAP1 protein, mouse