Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus

S. Iwata, K. Yamaoka, H. Niiro, S. Jabbarzadeh-Tabrizi, S. P. Wang, M. Kondo, M. Yoshikawa, K. Akashi, Yoshiya Tanaka

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Abstract

Objective: Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown. Methods: Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients. Results: Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-naïve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression. Conclusion: Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.

Original languageEnglish
Pages (from-to)695-704
Number of pages10
JournalLupus
Volume24
Issue number7
DOIs
Publication statusPublished - Jun 3 2015

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TNF Receptor-Associated Factor 6
Systemic Lupus Erythematosus
B-Lymphocytes
Phosphorylation
Tissue Donors
Blood Cells
Flow Cytometry

All Science Journal Classification (ASJC) codes

  • Rheumatology

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Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus. / Iwata, S.; Yamaoka, K.; Niiro, H.; Jabbarzadeh-Tabrizi, S.; Wang, S. P.; Kondo, M.; Yoshikawa, M.; Akashi, K.; Tanaka, Yoshiya.

In: Lupus, Vol. 24, No. 7, 03.06.2015, p. 695-704.

Research output: Contribution to journalArticle

Iwata, S, Yamaoka, K, Niiro, H, Jabbarzadeh-Tabrizi, S, Wang, SP, Kondo, M, Yoshikawa, M, Akashi, K & Tanaka, Y 2015, 'Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus', Lupus, vol. 24, no. 7, pp. 695-704. https://doi.org/10.1177/0961203314560424
Iwata, S. ; Yamaoka, K. ; Niiro, H. ; Jabbarzadeh-Tabrizi, S. ; Wang, S. P. ; Kondo, M. ; Yoshikawa, M. ; Akashi, K. ; Tanaka, Yoshiya. / Increased Syk phosphorylation leads to overexpression of TRAF6 in peripheral B cells of patients with systemic lupus erythematosus. In: Lupus. 2015 ; Vol. 24, No. 7. pp. 695-704.
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abstract = "Objective: Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown. Methods: Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients. Results: Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-na{\"i}ve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression. Conclusion: Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.",
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AU - Iwata, S.

AU - Yamaoka, K.

AU - Niiro, H.

AU - Jabbarzadeh-Tabrizi, S.

AU - Wang, S. P.

AU - Kondo, M.

AU - Yoshikawa, M.

AU - Akashi, K.

AU - Tanaka, Yoshiya

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N2 - Objective: Activation of B cells is a hallmark of systemic lupus erythematosus (SLE). Syk and TRAF6 are key signaling molecules in B-cell activation through BCR and CD40/TLR, respectively. Nevertheless, whether expression of Syk and TRAF6 is altered in SLE B cells remains unknown. Methods: Phosphorylation and/or expression of Syk and TRAF6 were analyzed by flow cytometry in peripheral blood mononuclear cells isolated from SLE patients. Results: Pronounced phosphorylation and expression of Syk were noted in B cells from SLE patients compared with healthy donors. Levels of Syk phosphorylation correlated with the disease activity score. TRAF6 was significantly over-expressed in B cells of SLE patients as compared with healthy donors, and significant correlation of levels of TRAF6 expression and Syk phosphorylation was observed in SLE patients. Levels of TRAF6 expression were more pronounced in CD27+ memory B cells than in CD27-naïve B cells. In vitro treatment of SLE B cells with a Syk inhibitor (BAY61-3606) reduced Syk phosphorylation as well as TRAF6 expression. Conclusion: Our results suggest that the activated Syk-mediated TRAF6 pathway leads to aberrant activation of B cells in SLE, and also highlight Syk as a potential target for B-cell-mediated processes in SLE.

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