Activation profile of Toll-like receptors of peripheral blood lymphocytes in patients with systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease associated with aberrant activation of T and B lymphocytes for the production of inflammatory cytokines and autoreactive antibodies. Animal studies of SLE have indicated that Toll-like receptors (TLR) are important in the pathogenesis of murine lupus. In the present clinical study, differential protein expressions of TLR-1-9 of monocytes and different lymphocyte subsets from patients with SLE and normal control subjects were determined by flow cytometry. Results showed that the expression of intracellular TLRs (TLR-3, -8, -9) and extracellular TLRs (TLR-1, -2, -4, -5, -6) were elevated in monocytes, CD4(+) T lymphocytes, CD8(+) T lymphocytes and B lymphocytes of SLE patients compared to control subjects (all P < 0.001). Moreover, cell surface expression of TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes, and TLR-6 on B lymphocytes, were correlated positively with SLE disease activity index (SLEDAI) (TLR-4 on CD4(+) T lymphocytes and CD8(+) T lymphocytes: r = 0.536, P = 0.04; r = 0.713, P = 0.003; TLR-6 in B lymphocytes: r = 0.572, P = 0.026). In concordance with the above results, there is an observable increased relative induction (%) of inflammatory cytokine interleukin (IL)-1beta, IL-6, IL-10 and IL-12, chemokines CCL2, CXCL8, CCL5 and CXCL10 from peripheral blood mononuclear cells (PBMC) upon differential stimulation by PolyIC (TLR-3 ligand), lipopolysaccharide (TLR-4 ligand), peptidoglycan (TLR-2 ligand), flagellin (TLR-5 ligand), R837 (TLR-7 ligand) and CpG DNA (TLR-9 ligand) in SLE patients compared to controls. These results suggest that the innate immune response for extracellular pathogens and self-originated DNA plays immunopathological roles via TLR activation in SLE.
Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
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D000328:Adult; D000634:Aminoquinolines / Q000494:pharmacology; D001402:B-Lymphocytes / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D015226:Dinucleoside Phosphates / Q000494:pharmacology; D005260:Female; D005408:Flagellin / Q000494:pharmacology; D006801:Humans; D000077271:Imiquimod; D007113:Immunity, Innate / Q000276:immunology; D007369:Interferon Inducers / Q000494:pharmacology; D007378:Interleukins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000276:immunology* / Q000503:physiopathology*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D010457:Peptidoglycan / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D012313:RNA / Q000494:pharmacology; D012720:Severity of Illness Index; D051193:Toll-Like Receptors / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D000634:Aminoquinolines; D018925:Chemokines; D015226:Dinucleoside Phosphates; D005408:Flagellin; D000077271:Imiquimod; D007369:Interferon Inducers; D007378:Interleukins; D008070:Lipopolysaccharides; D010457:Peptidoglycan; D011070:Poly I-C; D012313:RNA; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C015772:CpG dinucleotide