title: TLR cross-talk specifically regulates cytokine production by B cells from chronic inflammatory disease patients.
abstract: Chronic systemic inflammation links periodontal disease and diabetes to increased incidence of serious comorbidities. Activation of TLRs, particularly TLR2 and TLR4, promotes chronic systemic inflammation. Human B cells have been generally thought to lack these TLRs. However, recent work showed that an increased percentage of circulating B cells from inflammatory disease patients express TLR2 and TLR4, and that TLR engagement on B cells resulted in unexpected changes in gene expression. New data show that B cells from inflammatory disease patients secrete multiple cytokines in response to different classes of TLR ligands. Furthermore, the B cell response to combinations of TLR ligands is cytokine- and ligand-specific. Some cytokines (IL-1beta and IL-10) are predominantly regulated by TLR4, but others (IL-8 and TNF-alpha) are predominantly regulated by TLR2, due in part to TLR-dictated changes in transcription factor/promoter association. TLR2 and TLR9 also regulate B cell TLR4 expression, demonstrating that TLR cross-talk controls B cell responses at multiple levels. Parallel examination of B cells from periodontal disease and diabetes patients suggested that outcomes of TLR cross-talk are influenced by disease pathology. We conclude that disease-associated alteration of B cell TLR responses specifically regulates cytokine production and may influence chronic inflammation.
authors.affiliation: Department of Pathology, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Madhumita
authors.initials: M
authors.lastname: Jagannathan
authors.forename: Hatice
authors.initials: H
authors.lastname: Hasturk
authors.forename: Yanmei
authors.initials: Y
authors.lastname: Liang
authors.forename: Hyunjin
authors.initials: H
authors.lastname: Shin
authors.forename: Jeremy T
authors.initials: JT
authors.lastname: Hetzel
authors.forename: Alpdogan
authors.initials: A
authors.lastname: Kantarci
authors.forename: Daniel
authors.initials: D
authors.lastname: Rubin
authors.forename: Marie E
authors.initials: ME
authors.lastname: McDonnell
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Van Dyke
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Ganley-Leal
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Nikolajczyk
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D055113:Chronic Periodontitis / Q000276:immunology* / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis*; D005434:Flow Cytometry; D006801:Humans; D020239:Receptor Cross-Talk / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology* / Q000378:metabolism
chemical_list: D016207:Cytokines; D051193:Toll-Like Receptors