Cutting Edge: TLR2 Signaling in B Cells Promotes Autoreactivity to DNA via IL-6 Secretion
SISIRAK, Vanja
Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
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Immunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
Language
EN
Article de revue
This item was published in
Journal of Immunology. 2023-11, vol. 211, n° 10, p. 1475-1480
English Abstract
Autoantibodies to chromatin and dsDNA are a hallmark of systemic lupus erythematosus (SLE). In a mouse model of monogenic human SLE caused by DNASE1L3 deficiency, the anti-DNA response is dependent on endosomal nucleic ...Read more >
Autoantibodies to chromatin and dsDNA are a hallmark of systemic lupus erythematosus (SLE). In a mouse model of monogenic human SLE caused by DNASE1L3 deficiency, the anti-DNA response is dependent on endosomal nucleic acid-sensing TLRs TLR7 and TLR9. In this study, we report that this response also required TLR2, a surface receptor for microbial products that is primarily expressed on myeloid cells. Cell transfers into lymphopenic DNASE1L3-deficient mice showed that TLR2 was required for anti-DNA Ab production by lymphocytes. TLR2 was detectably expressed on B cells and facilitated the production of IL-6 by B cells activated in the presence of microbial products. Accordingly, treatment with broadspectrum antibiotics or Ab-mediated blockade of IL-6 delayed the anti-DNA response in DNASE1L3-deficient mice. These studies reveal an unexpected B cell_intrinsic role of TLR2 in systemic autoreactivity to DNA, and they suggest that microbial products may synergize with self- DNA in the activation of autoreactive B cells in SLERead less <
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