Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells

Prete, Francesca; Catucci, Marco; Labrada, Mayrel; Gobessi, Stefania; Castiello, Maria Carmina; Bonomi, Elisa; Aiuti, Alessandro; Vermi, William; Cancrini, Caterina; Metìn, Ayşe; Hambleton, Sophie; Bredius, Robbert G. M.; Notarangelo, Luigi D.; Burg, Mirjam van der; Kalinke, Ulrich; Villa, Anna; Benvenuti, Federica

doi:10.1083/jcb2003oia6

Cited by 2 publications

(2 citation statements)

References 62 publications

(70 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings further support the model in which BCR binding to self-antigens plays a key role in the induction of tolerance mechanisms, such as receptor editing or deletion, leading to the silencing of autoreactive B cells. The modest increase in TLR7 and TLR9 responses in human WASp-deficient B cells is a feature that has been previously reported in murine B cells, as well as plasmacytoid DCs (9,37), and that may also contribute to the increased removal of autoreactive clones at the central B cell tolerance checkpoint. In conclusion, WASp expression in developing B cells is important to establish proper thresholds for autoreactive B cell silencing in the BM.…”

Section: Discussionmentioning

confidence: 71%

Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients

Pala¹,

Morbach²,

Castiello³

et al. 2015

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 71%

Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients

Pala¹,

Morbach²,

Castiello³

et al. 2015

Journal of Clinical Investigation

Self Cite

View full text Add to dashboard Cite

“…These apparent discrepancies may be reconciled with the observation that other blood lineages, in particular regulatory T cells and plasmacytoid dendritic cells, play important, WASP-dependent roles in immune homeostasis, [21][22][23][24] independently of autoantibody production. 25 In conclusion, our data broaden the understanding of the molecular mechanisms underlying immune dysregulation in WAS and suggest that N-WASP may be an attractive novel target for pharmacological control of autoimmunity in patients with this disease.…”

Section: Methodsmentioning

confidence: 99%

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

Volpi

Santori

Abernethy

et al. 2016

Blood

View full text Add to dashboard Cite

By generating a mouse lacking expression of the WAS protein (WASP) selectively in B lymphocytes (B/WcKO), we and others have revealed a nonredundant B-cell-intrinsic role of WASP in immune homeostasis and prevention of autoimmunity, as well as in marginal zone (MZ) development and regulation of the germinal center (GC) reaction.3-5 Neural WASP (N-WASP, encoded by the Wasl gene) is another member of the WASP family of proteins; it is ubiquitously expressed and shares 50% homology with WASP.6 Similar to WASP, N-WASP undergoes a conformational change upon activation that enables initiation of actin polymerization, 7,8 thereby linking cellular activation to cytoskeletal modifications. 9 Selective deletion of N-WASP in B lymphocytes of Was knockout (WKO) mice resulted in the aggravation of B-cell abnormalities, including a strong decrease of intracellular calcium flux and Bruton's tyrosine kinase (Btk) and Src homology 2-containing inositol 59 phosphatase phosphorylation upon B-cell receptor (BCR) stimulation, 10 further worsening of MZ B-cell depletion, 11 and defective somatic hypermutation. 12 However, lack of WASP expression in multiple hematopoietic cells may have indirectly contributed to B-cell abnormalities in these models.To investigate the B-cell intrinsic role played by WASP and N-WASP in immune homeostasis and regulation more specifically, we have developed a double conditional mouse model (B/DcKO) in which deletion of both Was and Wasl floxed alleles in B lymphocytes is driven by the Cre recombinase expressed under the B-cell-specific promoter mb1. Here we show that deletion of N-WASP in B cells impairs B-cell activation and T-cell-dependent antibody responses and

show abstract

Wiskott-Aldrich syndrome protein–mediated actin dynamics control type-I interferon production in plasmacytoid dendritic cells

Cited by 2 publications

References 62 publications

Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients

Lentiviral-mediated gene therapy restores B cell tolerance in Wiskott-Aldrich syndrome patients

N-WASP is required for B-cell–mediated autoimmunity in Wiskott-Aldrich syndrome

Contact Info

Product

Resources

About