Pubblicazioni

Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation.  (2013)

Autori:
Lamagna, C; Scapini, Patrizia; van Ziffle, Ja; Defranco, Al; Lowell, Ca
Titolo:
Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation.
Anno:
2013
Tipologia prodotto:
Articolo in Rivista
Tipologia ANVUR:
Articolo su rivista
Lingua:
Inglese
Referee:
No
Nome rivista:
Proceedings of the National Academy of Sciences of the United States of America
ISSN Rivista:
0027-8424
N° Volume:
110
Numero o Fascicolo:
35
Intervallo pagine:
E3311-E3320
Parole chiave:
Lyn tyrosine kinase; conditional dendritic cell mutants; interleukin 1 signaling; lipopolysacchride signaling
Breve descrizione dei contenuti:
Deletion of lyn, a Src-family tyrosine kinase expressed by B, myeloid, and dendritic cells (DCs), triggers lupus-like disease in mice, characterized by autoantibody production and renal immune complex deposition leading to chronic glomerulonephritis. B cells from these mice are hyperactive to antigen-receptor stimulation owing to a loss of inhibitory signaling mediated by Lyn kinase. The hyperactive B-cell responses are thought to underlie the development of autoimmunity in this model. Lyn-deficient mice also manifest significant myeloexpansion. To test the contribution of different immune cell types to the lupus-like disease in this model, we generated a lyn(flox/flox) transgenic mouse strain. To our surprise, when we crossed these mice to Cd11c-cre animals, generating DC-specific deletion of Lyn, the animals developed spontaneous B- and T-cell activation and subsequent production of autoantibodies and severe nephritis. Remarkably, the DC-specific Lyn-deficient mice also developed severe tissue inflammatory disease, which was not present in the global lyn(-/-) strain. Lyn-deficient DCs were hyperactivated and hyperresponsive to Toll-like receptor agonists and IL-1β. To test whether dysregulation of these signaling pathways in DCs contributed to the inflammatory/autoimmune phenotype, we crossed the lyn(f/f) Cd11c-cre(+) mice to myd88(f/f) animals, generating double-mutant mice lacking both Lyn and the adaptor protein myeloid differentiation factor 88 (MyD88) in DCs, specifically. Deletion of MyD88 in DCs alone completely reversed the inflammatory autoimmunity in the DC-specific Lyn-mutant mice. Thus, we demonstrate that hyperactivation of MyD88-dependent signaling in DCs is sufficient to drive pathogenesis of lupus-like disease, illuminating the fact that dysregulation in innate immune cells alone can lead to autoimmunity.
Id prodotto:
79850
Handle IRIS:
11562/670159
depositato il:
21 febbraio 2014
ultima modifica:
12 novembre 2022
Citazione bibliografica:
Lamagna, C; Scapini, Patrizia; van Ziffle, Ja; Defranco, Al; Lowell, Ca, Hyperactivated MyD88 signaling in dendritic cells, through specific deletion of Lyn kinase, causes severe autoimmunity and inflammation. «Proceedings of the National Academy of Sciences of the United States of America» , vol. 110 , n. 352013pp. E3311-E3320

Consulta la scheda completa presente nel repository istituzionale della Ricerca di Ateneo IRIS

Progetti Collegati
Titolo Dipartimento Responsabili
<<indietro

Attività

Strutture

Condividi