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Modulation of Toll-like receptor 9 expression in systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease of unknown etiology characterized by the presence of autoreactive antibodies to own DNA and other nuclear antigens. The mode by which autoreactive B cells defy mechanisms of peripheral tolerance is still unclear. One way of induction and survival of autoreactive B cells could be through activation of Toll-like receptors (TLR). TLR recognize invading microorganisms, and infections have been known to trigger and/or aggravate SLE. As TLR9 is intracellular receptor for unmethylated DNA, we investigated the expression of TLR9 in peripheral blood of newly-discovered SLE patients by flow cytometry using three or four-color immunofluorescence staining. Patients were analyzed before therapy, three weeks after the onset of glucocorticoid therapy, and again after three months, when chloroquine was introduced into the protocol and steroid dose gradually lowered. TLR9 expression in B cells was higher in patients on glucocorticoids than in controls. Upon introduction of chloroquine, TLR9 expression decreased to the levels observed in controls. The results of in vitro stimulation of isolated cells from healthy donors with dexamethasone and/or chloroquine were in accordance with TLR expression behavior in patients. Further experiments are under way to clarify the significance of TLR levels in SLE and possible immunomodulatory effects of drugs used in treatment.

TLR9; Toll-like receptors; autoimmunity; systemic lupus erythematosus

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