Novel CXCL13 transgenic mouse: inflammation drives pathogenic effect of CXCL13 in experimental myasthenia gravis

Oncotarget
Julia Miriam WeissRozen Le Panse

Abstract

Abnormal overexpression of CXCL13 is observed in many inflamed tissues and in particular in autoimmune diseases. Myasthenia gravis (MG) is a neuromuscular disease mainly mediated by anti-acetylcholine receptor autoantibodies. Thymic hyperplasia characterized by ectopic germinal centers (GCs) is a common feature in MG and is correlated with high levels of anti-AChR antibodies. We previously showed that the B-cell chemoattractant, CXCL13 is overexpressed by thymic epithelial cells in MG patients. We hypothesized that abnormal CXCL13 expression by the thymic epithelium triggered B-cell recruitment in MG. We therefore created a novel transgenic (Tg) mouse with a keratin 5 driven CXCL13 expression. The thymus of Tg mice overexpressed CXCL13 but did not trigger B-cell recruitment. However, in inflammatory conditions, induced by Poly(I:C), B cells strongly migrated to the thymus. Tg mice were also more susceptible to experimental autoimmune MG (EAMG) with stronger clinical signs, higher titers of anti-AChR antibodies, increased thymic B cells, and the development of germinal center-like structures. Consequently, this mouse model finally mimics the thymic pathology observed in human MG. Our data also demonstrated that inflammation is m...Continue Reading

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Citations

May 22, 2016·Clinical Reviews in Allergy & Immunology·Marieke RobinetRozen Le Panse
Nov 11, 2017·Annals of the New York Academy of Sciences·Mélanie A CronRozen Le Panse
Jan 11, 2020·Frontiers in Immunology·Shanshan LuoDesheng Hu
Mar 11, 2020·Frontiers in Immunology·Ruksana Huda
Jun 7, 2019·JCI Insight·Ariel D StockChaim Putterman
Oct 10, 2020·Journal of Neuroinflammation·Mélanie A CronRozen Le Panse
Mar 19, 2021·Frontiers in Immunology·Yonas Bekele FeyissaJay A Berzofsky
Sep 26, 2021·Neurology. Neuroimmunology and Neuroinflammation·Yohei YamamotoYuishin Izumi

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Methods Mentioned

BETA
transgenic
ELISA
Flow
flow cytometry
biopsy
ELISAs
transfection
PCR
light microscopy
FACS

Software Mentioned

AxioVision

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