1303 Bacterial DNA induces regulatory B cells and attenuates lupus through a B cell-extrinsic, TLR9-dependent mechanism
نویسندگان
چکیده
Our recent study has demonstrated induction of regulatory B cells (Bregs) by bacterial DNA in MRL/lpr mice leading to attenuation SLE. This suggests a role for the gut bacteria SLE development. However, mechanism which induces Breg cell differentiation remains be elucidated. Bacterial contains unmethylated CpG motifs are recognized innate immune molecule, toll-like receptor 9 (TLR9). We therefore hypothesize that bacteria-derived Bregs TLR9-dependent manner, turn protects against lupus initiation. To test our hypothesis, TLR9 global knockout (Tlr9-/-) and their heterozygous (Tlr9+/-) littermates were randomized into 2 groups per genotype. Beginning at 4 weeks age, one group each genotype received 80 µg E. coli double- stranded (dsDNA) once week oral gavage consecutive weeks, whereas other phosphate buffered saline (PBS) as control. Urine samples collected before euthanasia blood, spleen, lymph nodes, kidneys processed following 15 age. In vitro culture treatment with was used investigate TLR9-dependent, cell-intrinsic or -extrinsic induction. data showed trend decrease proteinuria, well sizes spleen Tlr9+/- mice. Interestingly, serum levels anti-dsDNA IgM, been shown protective lupus, significantly increased DNA-treated mice, although pathogenic IgG remained unchanged. Additionally, flow cytometry analysis splenocytes an increasing percentage interleukin-10 positive (IL-10+) concomitant double negative (DN, CD4-CD8-) T cells. In kidney, also decreased CD45+ Importantly, all DNA- induced changes observed including those organ weight, splenic Bregs, DN renal cells, abrogated Tlr9-/- cocultures non-B from Tlr9+/+ revealed but cell-extrinsic, mediated IL-6 produced most likely myeloid Altogether, possible through involves IL-10+ secretion potentially anti- dsDNA IgM.
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ژورنال
عنوان ژورنال: Microbiome
سال: 2022
ISSN: ['2049-2618']
DOI: https://doi.org/10.1136/lupus-2022-lupus21century.93