Pubblicazioni

Autori:

Hua, Z; Gross, Aj; Lamagna, C; Ramos Hernández, N; Scapini, Patrizia; Ji, M; Shao, H; Lowell, Ca; Hou, B; Defranco, Al

Titolo:

Requirement for MyD88 Signaling in B Cells and Dendritic Cells for Germinal Center Anti-Nuclear Antibody Production in Lyn-Deficient Mice.

Anno:

2014

Tipologia prodotto:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Lingua:

Inglese

Referee:

Sì

Nome rivista:

Journal of Immunology

ISSN Rivista:

0022-1767

N° Volume:

192

Numero o Fascicolo:

3

Intervallo pagine:

875-885

Parole chiave:

immunology; Myd88; B cells; myeloid cells; Lyn(-/-) mice; lupus erythematosus

Breve descrizione dei contenuti:

The intracellular tyrosine kinase Lyn mediates inhibitory receptor function in B cells and myeloid cells, and Lyn(-/-) mice spontaneously develop an autoimmune and inflammatory disease that closely resembles human systemic lupus erythematosus. TLR-signaling pathways have been implicated in the production of anti-nuclear Abs in systemic lupus erythematosus and mouse models of it. We used a conditional allele of Myd88 to determine whether the autoimmunity of Lyn(-/-) mice is dependent on TLR/MyD88 signaling in B cells and/or in dendritic cells (DCs). The production of IgG anti-nuclear Abs, as well as the deposition of these Abs in the glomeruli of the kidneys, leading to glomerulonephritis in Lyn(-/-) mice, were completely abolished by selective deletion of Myd88 in B cells, and autoantibody production and glomerulonephritis were delayed or decreased by deletion of Myd88 in DCs. The reduced autoantibody production in mice lacking MyD88 in B cells or DCs was accompanied by a dramatic decrease in the spontaneous germinal center (GC) response, suggesting that autoantibodies in Lyn(-/-) mice may depend on GC responses. Consistent with this view, IgG anti-nuclear Abs were absent if T cells were deleted (TCRβ(-/-) TCRδ(-/-) mice) or if T cells were unable to contribute to GC responses as the result of mutation of the adaptor molecule SAP. Thus, the autoimmunity of Lyn(-/-) mice was dependent on T cells and on TLR/MyD88 signaling in B cells and in DCs, supporting a model in which DC hyperactivity combines with defects in tolerance in B cells to lead to a T cell-dependent systemic autoimmunity in Lyn(-/-) mice.

Id prodotto:

79849

Handle IRIS:

11562/670158

depositato il:

21 febbraio 2014

ultima modifica:

11 novembre 2022

Citazione bibliografica:

Hua, Z; Gross, Aj; Lamagna, C; Ramos Hernández, N; Scapini, Patrizia; Ji, M; Shao, H; Lowell, Ca; Hou, B; Defranco, Al, Requirement for MyD88 Signaling in B Cells and Dendritic Cells for Germinal Center Anti-Nuclear Antibody Production in Lyn-Deficient Mice. «Journal of Immunology» , vol. 192 , n. 3 , 2014 , pp. 875-885

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