BANK1 Controls the Development of SLE By Modulating TLR7 Signaling and Type I IFN-Induced Translation Initiation Pathway in B Cells

Ying-Yu Wu¹, Ramesh Kumar², Harini Bagavant¹ and Marta E. Alarcon Riquelme³, ¹Arthritis and Clinical Immunology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ²Oklahoma Medical Research Foundation, Oklahoma Cty, OK, ³Arthritis & Clinical Immunology, Oklahoma Medical Research Foundation, Center for Genomics and Oncological Research Pfizer-University of Granada-Junta de Andalucia, Oklahoma City, OK

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Animal models, B cells, interferons and toll-like receptors, SLE

Session Information

Date: Monday, November 9, 2015

Title: Systemic Lupus Erythematosus - Animal Models Poster I

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: BANK1 is a susceptibility gene for SLE, and we have shown that stimulation of TLR9 agonist leads to a reduction in the activation of the translation initiation pathway. Here we investigated the effects of the adaptor Bank1 in TLR7 signaling using the B6.Sle1.yaamouse, a lupus model that develops disease through exacerbated TLR7 expression.

Methods: Crosses of B6.Sle1.yaa with Bank1-/-mice were produced and studied for the development of disease and signaling following TLR7 and IFNa stimulation.

Results: Bank1 deficiency maintained several B and myeloid cell phenotypes close to normal wild-type levels. Most striking was the reduction in total serum IgG antibodies, but not of IgM, and reduced serum levels of autoantibodies, IL-6 and BAFF, features accompanied by reduced mortality. Purified B cells from Bank1 deficient mice had strongly reduced IFNb, Irf7, Aicda and Stat1 gene expression following TLR7 agonist stimulation. Furthermore, phosphorylation of the transcription factor STAT1 was impaired as was the nuclear translocation of IRF7, a key molecule in TLR7 signaling. As the optimal function of B cells depends on type I interferon, we investigated if Bank1deficiency had effects on the IFNAR signaling pathway. We demonstrate that BANK1 controls activation of the eIF4E translation initiation pathway induced by type I IFN, hence controlling interferon-inducible genes.

Conclusion: Our results show that BANK1 controls TLR7 and IFNAR signaling in B cells, modulating transcription and translation initiation events, respectively, and contributing to autoimmune disease development.

Disclosure: Y. Y. Wu, None; R. Kumar, None; H. Bagavant, None; M. E. Alarcon Riquelme, None.

To cite this abstract in AMA style:

Wu YY, Kumar R, Bagavant H, Alarcon Riquelme ME. BANK1 Controls the Development of SLE By Modulating TLR7 Signaling and Type I IFN-Induced Translation Initiation Pathway in B Cells [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/bank1-controls-the-development-of-sle-by-modulating-tlr7-signaling-and-type-i-ifn-induced-translation-initiation-pathway-in-b-cells/. Accessed .

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