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Lack of IL-17 Receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice

Corneth, O. B. J., Schaper, F., Luk, F., Asmawidjaja, P. S., Mus, A. M. C., Horst, G., Heeringa, P., Hendriks, R. W., Westra, J. & Lubberts, E., Mar-2019, In : Scientific Reports. 9, 10 p., 4032.

Research output: Contribution to journalArticleAcademicpeer-review

  • Odilia B J Corneth
  • Fleur Schaper
  • Franka Luk
  • Patrick S Asmawidjaja
  • Adriana M C Mus
  • Gerda Horst
  • Peter Heeringa
  • Rudi W Hendriks
  • Johanna Westra
  • Erik Lubberts

Defects in Fas function correlate with susceptibility to systemic autoimmune diseases like autoimmune lymphoproliferative syndrome (ALPS) and systemic lupus erythematosus (SLE). C57BL/6 lpr (B6/lpr) mice are used as an animal model of ALPS and develop a mild SLE phenotype. Involvement of interleukin-17A (IL-17A) has been suggested in both phenotypes. Since IL-17 receptor A is part of the signaling pathway of many IL-17 family members we investigated the role of IL-17 receptor signaling in disease development in mice with a B6/lpr background. B6/lpr mice were crossed with IL-17 receptor A deficient (IL-17RA KO) mice and followed over time for disease development. IL-17RA KO/lpr mice presented with significantly enhanced lymphoproliferation compared with B6/lpr mice, which was characterized by dramatic lymphadenomegaly/splenomegaly and increased lymphocyte numbers, expansion of double-negative (DN) T-cells and enhanced plasma cell formation. However, the SLE phenotype was not enhanced, as anti-nuclear antibody (ANA) titers and induction of glomerulonephritis were not different. In contrast, levels of High Mobility Group Box 1 (HMGB1) and anti-HMGB1 autoantibodies were significantly increased in IL-17RA KO/lpr mice compared to B6/lpr mice. These data show that lack of IL-17RA signaling aggravates the lymphoproliferative phenotype in B6/lpr mice but does not affect the SLE phenotype.

Original languageEnglish
Article number4032
Number of pages10
JournalScientific Reports
Volume9
Publication statusPublished - Mar-2019

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