Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation

Lougaris, Vassilios; Baronio, Manuela; Vitali, Massimiliano; Tampella, Giacomo; Cattalini, Marco; Tassone, Laura; Soresina, Annarosa; Badolato, Raffaele; Plebani, Alessandro

doi:10.1016/j.jaci.2013.12.1085

Cited by 64 publications

(53 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies on patients with XLA [7–9] showed the involvement of BTK in innate immune cell responses [48] and its role in human DC responses upon TLR9 engagement [49]. Moreover, studies on the immune function of XLA patients who lack functional BTK might also provide information concerning the consequences of drugs acting as BTK inhibitors on innate immunity of patients under these new treatments [50–54].…”

Section: Discussionmentioning

confidence: 99%

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

et al. 2017

View full text Add to dashboard Cite

The lack of BTK in X-linked agammaglobulinemia (XLA) patients does not affect monocytes and polymorphonuclear cells (PMN) phenotype and functions. In this study, we show that XLA patients had an increased frequency of the intermediate monocytes subset and that BTK-deficient monocytes and PMN had a normal expression of receptors involved in the activation and cellular responses. We demonstrate that BTK is not required for migration, phagocytosis and the production of reactive oxygen species (ROS) following engagement of FC gamma receptors (FcγR). XLA monocytes and PMN showed an efficient calcium (Ca2+)-independent activation of oxidative burst, suggesting that oxidative burst is less dependent by Ca2+ mobilization. The phagocytosis was functional and it remained unaltered also after Ca2+ chelation, confirming the independence of phagocytosis on Ca2+ mobilization. Intravenous immunoglobulin (IVIg) infusion exerted an anti-inflammatory effect by reducing the frequency of pro-inflammatory monocytes. In monocytes, the IVIg reduce the oxidative burst and phagocytosis even if these functions remained efficient.

show abstract

Section: Discussionmentioning

confidence: 99%

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

et al. 2017

View full text Add to dashboard Cite

show abstract

“…The most common autoimmune conditions are arthritis, insulin-dependent diabetes mellitus, AHA and scleroderma [17]. Abnormal tolllike receptor (TLR) 9 signaling through NF-kB [18,19] and dendritic cell deficits may contribute to the predisposition ot autoimmunity in X-linked agammaglobulinemia because BTK, the protein affected in this disease, modulates TLR signalling [20,21]. The most likely cause, however, is that B-cells cannot signal effectively and fail to undergo central tolerance in the bone marrow [22][23][24].…”

Section: Key Pointsmentioning

confidence: 99%

The intersection of immune deficiency and autoimmunity

Maggadóttir

Sullivan

2014

Current Opinion in Rheumatology

View full text Add to dashboard Cite

show abstract

“…Indeed, macrophages, neutrophils, dendritic cells and mast cells also express BTK (51, 68–71), although its role is not well-defined in those cell types. Some TLR responses are aberrant in the absence of BTK, which could contribute to susceptibility to infectious diseases (72, 73). In addition, overproduction of inflammatory cytokines in response to TLR signaling has been reported, which could contribute to inflammation in XLA patients (74, 75).…”

Section: Introductionmentioning

confidence: 99%

The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy

Crofford

Nyhoff

Sheehan

et al. 2016

Expert Review of Clinical Immunology

117

114

View full text Add to dashboard Cite

Summary Bruton’s tyrosine kinase (BTK) mediates B cell signaling and is also present in innate immune cells but not T cells. BTK propagates B cell receptor (BCR) responses to antigen-engagement as well as to stimulation via CD40, toll-like receptors (TLRs), Fc receptors (FCRs) and chemokine receptors. Importantly, BTK can modulate signaling, acting as a “rheostat” rather than an “on-off” switch; thus, overexpression leads to autoimmunity while decreased levels improve autoimmune disease outcomes. Autoreactive B cells depend upon BTK for survival to a greater degree than normal B cells, reflected as loss of autoantibodies with maintenance of total antibody levels when BTK is absent. This review describes contributions of BTK to immune tolerance, including studies testing BTK-inhibitors for treatment of autoimmune diseases.

show abstract

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation

Cited by 64 publications

References 24 publications

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

The lack of BTK does not impair monocytes and polymorphonuclear cells functions in X-linked agammaglobulinemia under treatment with intravenous immunoglobulin replacement

The intersection of immune deficiency and autoimmunity

The role of Bruton’s tyrosine kinase in autoimmunity and implications for therapy

Contact Info

Product

Resources

About