IL-17 activates the canonical NF-kappaB signaling pathway in autoimmune B cells of BXD2 mice to upregulate the expression of regulators of G-protein signaling 16

J Immunol. 2010 Mar 1;184(5):2289-96. doi: 10.4049/jimmunol.0903133. Epub 2010 Feb 5.


We previously identified that autoreactive B cells from BXD2 mice can be targeted by IL-17, leading to upregulation of the expression of regulators of G-protein signaling (Rgs) genes that facilitated the development of spontaneous germinal centers. Little is known about the signaling pathway used by IL-17 to upregulate RGS. In the current study, we found that IL-17 rapidly activates the canonical NF-kappaB signaling pathway and that BXD2 B cells exhibit higher basal and activated phosphorylated p65 levels than B6 or BXD2-Il17ra(-/-) B cells. Inhibition of p65 phosphorylation downregulated RGS16 expression and abrogated the IL-17-induced chemotactic arrest of B cells in response to CXCL12. Knockdown of TNFR-associated factor 6 or NF-kappaB activator 1 in 70Z/3 pre-B cells led to decreased Rgs16 expression, indicating that both of these two genes are involved in IL-17-mediated activation of NF-kappaB signaling in B cells. These findings identify the signaling pathway regulated by IL-17 to contribute to the development of spontaneous germinal centers in autoimmune BXD2 mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Autoimmunity
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • Blotting, Western
  • Cell Line
  • Cell Nucleus / metabolism
  • Female
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Interleukin-17 / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • NF-kappa B / metabolism*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • RNA Interference
  • Receptors, Interleukin-17 / genetics
  • Receptors, Interleukin-17 / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism
  • Up-Regulation / drug effects


  • Adaptor Proteins, Signal Transducing
  • Il17ra protein, mouse
  • Interleukin-17
  • NF-kappa B
  • RGS Proteins
  • RGS16 protein
  • Receptors, Interleukin-17
  • TNF Receptor-Associated Factor 6
  • Traf3ip2 protein, mouse