Genomics

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Regulation of dendritic cells and macrophages by an anti-apoptotic cell natural Ab that inhibits inflammatory arthritis


ABSTRACT: Although natural antibodies (NAbs) are present from birth, little is known about what drives their selection, and whether they have housekeeping functions. We now show that the prototypic T15-NAb, first identified because of its protective role in infection, is representative of a previously unknown type of NAb response that specifically recognizes and forms complexes with apoptotic cells, and which promotes cell-corpse engulfment by phagocytes. This T15-NAb-mediated process is dependent on the recruitment of C1q and mannose-binding lectin (MBL), which have known immune modulatory activities that also provide “eat me” signals for phagocytic clearance. Further investigation revealed that, the addition of T15-NAb significantly suppressed in vitro macrophage LPS-induced TNF-alpha and IL-6 secretion, as well as in vitro Toll-like receptor (TLR)-induced dendritic cell maturation and secretion of pro-inflammatory cytokines and chemokines. Significantly, high doses of this B-1 cell produced NAb also inhibited in vivo TLR–induced pro-inflammatory responses, and could suppress autoimmune inflammatory arthritis. These studies identify and characterize a previously unknown regulatory circuit by which a NAb product of innate-like B cells aids homeostasis by control of fundamental inflammatory pathways. Keywords: Dendritic cells, Macrophages, Natural Antibodies, Apoptosis, Inflammation, Arthritis

ORGANISM(S): Mus musculus Homo sapiens unidentified

PROVIDER: GSE14969 | GEO | 2009/08/25

SECONDARY ACCESSION(S): PRJNA111863

REPOSITORIES: GEO

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