CONCISE REVIEW
Toll-like receptors 7 and 9 in myasthenia gravis thymus: amplifiers of autoimmunity?
Paola Cavalcante,
Claudia Barzago,
Fulvio Baggi,
Carlo Antozzi,
Lorenzo Maggi,
Renato Mantegazza,
Pia Bernasconi,
Paola Cavalcante
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorClaudia Barzago
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorFulvio Baggi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorCarlo Antozzi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorLorenzo Maggi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorRenato Mantegazza
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorCorresponding Author
Pia Bernasconi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Address for correspondence: Dr. Pia Bernasconi, Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta,” Via Celoria 11, 20133 Milan, Italy. [email protected]Search for more papers by this authorPaola Cavalcante,
Claudia Barzago,
Fulvio Baggi,
Carlo Antozzi,
Lorenzo Maggi,
Renato Mantegazza,
Pia Bernasconi,
Paola Cavalcante
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorClaudia Barzago
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorFulvio Baggi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorCarlo Antozzi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorLorenzo Maggi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorRenato Mantegazza
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Search for more papers by this authorCorresponding Author
Pia Bernasconi
Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta”, Milan, Italy
Address for correspondence: Dr. Pia Bernasconi, Neurology IV, Neuroimmunology and Neuromuscular Diseases Unit, Fondazione Istituto Neurologico “Carlo Besta,” Via Celoria 11, 20133 Milan, Italy. [email protected]Search for more papers by this authorAbstract
Pathogen infections and dysregulated Toll-like receptor (TLR)–mediated innate immune responses are suspected to play key roles in autoimmunity. Among TLRs, TLR7 and TLR9 have been implicated in several autoimmune conditions, mainly because of their ability to promote abnormal B cell activation and survival. Recently, we provided evidence of Epstein–Barr virus (EBV) persistence and reactivation in the thymus of myasthenia gravis (MG) patients, suggesting an involvement of EBV in the intrathymic pathogenesis of the disease. Considerable data highlight the existence of pathogenic crosstalk among EBV, TLR7, and TLR9: EBV elicits TLR7/9 signaling, which in turn can enhance B cell dysfunction and autoimmunity. In this article, after a brief summary of data demonstrating TLR activation in MG thymus, we provide an overview on the contribution of TLR7 and TLR9 to autoimmune diseases and discuss our recent findings indicating a pivotal role for these two receptors, along with EBV, in driving, perpetuating, and/or amplifying intrathymic B cell dysregulation and autoimmune responses in MG. Development of therapeutic approaches targeting TLR7 and TLR9 signaling could be a novel strategy for treating the chronic inflammatory autoimmune process in myasthenia gravis.
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