Lack of IL-17 Receptor A signaling aggravates lymphoproliferation in C57BL/6 lpr mice
| Autor: | Adriana M. C. Mus, Fleur Schaper, Odilia B. J. Corneth, Erik Lubberts, Gerda Horst, Johanna Westra, Rudi W. Hendriks, Peter Heeringa, Franka Luk, Patrick S. Asmawidjaja |
|---|---|
| Přispěvatelé: | Pulmonary Medicine, Rheumatology, Groningen Kidney Center (GKC), Translational Immunology Groningen (TRIGR), Groningen Institute for Organ Transplantation (GIOT) |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
C57BL/6 Mice Inbred MRL lpr T-Lymphocytes lcsh:Medicine Plasma cell Kidney HMGB1 Article Mice 03 medical and health sciences 0302 clinical medicine immune system diseases medicine Animals Lupus Erythematosus Systemic HMGB1 Protein lcsh:Science Receptor skin and connective tissue diseases Cell Proliferation Mice Knockout B-Lymphocytes Receptors Interleukin-17 Multidisciplinary biology business.industry Autoimmune Lymphoproliferative Syndrome lcsh:R Autoantibody Glomerulonephritis medicine.disease biology.organism_classification Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Autoimmune lymphoproliferative syndrome Immunology biology.protein lcsh:Q Lymph Nodes Antibody business Spleen 030217 neurology & neurosurgery |
| Zdroj: | Scientific Reports, 9:4032. Nature Publishing Group Scientific Reports, Vol 9, Iss 1, Pp 1-10 (2019) Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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