Differential expression of Cathepsin E in transthyretin amyloidosis: from neuropathology to the immune system.

Résumé : Background: Increasing evidence supports a key role for inflammation in the neurodegenerative process of familial amyloidotic polyneuropathy (FAP). While there seems to be an overactivation of the neuronal interleukin-1 signaling pathway, the immune response is apparently compromised in FAP. Accordingly, little immune cell infiltration is observed around pre-fibrillar or fibrillar amyloid deposits, with the underlying mechanism for this phenomenon remaining poorly understood. Cathepsin E (CtsE) is an important intermediate for antigen presentation and chemotaxis, but its role in the pathogenesis of FAP disease remains unknown. Methods: In this study, we used both mouse primary macrophages and in vivo studies based on transgenic models of FAP and human samples to characterize CtsE expression in different physiological systems. Results: We show that CtsE is critically decreased in bone marrow-derived macrophages from a FAP mouse model, possibly contributing for cell function impairment. Compromised levels of CtsE were also found in injured nerves of transgenic mice and, most importantly, in naïve peripheral nerves, sensory ganglia, murine stomach, and sural nerve biopsies derived from FAP patients. Expression of CtsE in tissues was associated with transthyretin (TTR) deposition and differentially regulated accordingly with the physiological system under study. Preventing deposition with a TTR small interfering RNA rescued CtsE in the peripheral nervous system (PNS). In contrast, the expression of CtsE increased in splenic cells (mainly monocytes) or peritoneal macrophages, indicating a differential macrophage phenotype. Conclusion: Altogether, our data highlights the potential of CtsE as a novel FAP biomarker and a possible modulator for innate immune cell chemotaxis to the disease most affected tissues-the peripheral nerve and the gastrointestinal tract.
Type de document :
Article dans une revue
Journal of Neuroinflammation, BioMed Central, 2017, 14 (1), pp.115. 〈10.1186/s12974-017-0891-9〉
Liste complète des métadonnées

Littérature citée [55 références]  Voir  Masquer  Télécharger

Contributeur : Marie-Christine Vougny <>
Soumis le : mardi 6 juin 2017 - 17:12:57
Dernière modification le : jeudi 8 juin 2017 - 09:35:03


Publication financée par une institution


Distributed under a Creative Commons Paternité 4.0 International License




Nádia Pereira Gonçalves, João Moreira, Diana Martins, Paulo Vieira, Laura Obici, et al.. Differential expression of Cathepsin E in transthyretin amyloidosis: from neuropathology to the immune system.. Journal of Neuroinflammation, BioMed Central, 2017, 14 (1), pp.115. 〈10.1186/s12974-017-0891-9〉. 〈pasteur-01533696〉



Consultations de la notice


Téléchargements de fichiers