Role of DAMPs and cell death in autoimmune diseases: the example of multiple sclerosis.
Genes Immun
; 24(2): 57-70, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36750753
ABSTRACT
Multiple sclerosis is a chronic neuroinflammatory demyelinating disease of the central nervous system (CNS) of unknown etiology and still incompletely clarified pathogenesis. The disease is generally considered a disorder resulting from a complex interplay between environmental risk factors and predisposing causal genetic variants. To examine the etiopathogenesis of the disease, two complementary pre-clinical models are currently discussed the "outside-in" model proposing a peripherally elicited inflammatory/autoimmune attack against degraded myelin as the cause of the disease, and the "inside-out" paradigm implying a primary cytodegenerative process of cells in the CNS that triggers secondary reactive inflammatory/autoimmune responses against myelin debris. In this review, the integrating pathogenetic role of damage-associated molecular patterns (DAMPs) in these two scenario models is examined by focusing on the origin and sources of these molecules, which are known to promote neuroinflammation and, via activation of pattern recognition receptor-bearing antigen-presenting cells, drive and shape autoimmune responses. In particular, environmental factors are discussed that are conceptually defined as agents which produce endogenous DAMPs via induction of regulated cell death (RCD) or act themselves as exogenous DAMPs. Indeed, in the field of autoimmune diseases, including multiple sclerosis, recent research has focused on environmental triggers that cause secondary events in terms of subroutines of RCD, which have been identified as prolific sources of DAMPs. Finally, a model of a DAMP-driven positive feed-forward loop of chronic inflammatory demyelinating processes is proposed, aimed at reconciling the competing "inside-out" and "outside-in" paradigms.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes
/
Alarminas
/
Esclerose Múltipla
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Genes Immun
Assunto da revista:
ALERGIA E IMUNOLOGIA
/
BIOLOGIA MOLECULAR
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Alemanha