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Role of Bank1 in the Secretion of IL6 and Expression of Type I Interferon Inducible Genes Through the Control of p38 Signaling and the eIF4E Translation Initiation Complex

ABSTRACT: Bank1 is an adaptor protein primarily expressed in B-cells with a little understood role in B-cell signaling. Studies involving human systemic lupus erythematosus showed that genetic variants in the human BANK1 gene were associated with SLE. Our studies have suggested that BANK1 could have an endosomal intracellular localization suggesting that it could play a role in endosomal-dependent signaling induced by nucleic acids such as the Tlr9 agonist CpG. To investigate this we used a Bank1 deficient mouse. Deficiency of Bank1 led to an important reduction in p38 phosphorylation, without affecting Erk or Jnk after CpG stimulation, and a reduction in IL-6 production. In addition, our data demonstrates the reduced transcription and phosphorylation of eIF4E and reduced phosphorylation of the MAP kinase signal-integrating kinases Mnk1/2, confirming the effect on molecules that are direct targets of p38 that are also involved in protein translation initiation. Furthermore, Bank1 deficient B-cells show stronger up- and down-regulation of type-1 interferon response genes and genes repressed during such responsesupregulation of interferon response genes. Our data clearly shows that Bank1 has previously unrecognized and specific roles in the CpG-induced production of IL-6 by splenic B lymphocytes via p38 signaling and suggests a unique role that involves the regulation of the translation initiation complex and type 1 interferon responses of major impact in viral infections and autoimmunity.

ORGANISM(S): Mus musculus

PROVIDER: GSE41376 | GEO | 2014/12/13

SECONDARY ACCESSION(S): PRJNA176716

REPOSITORIES: GEO

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