engleski

THE ROLE OF TOLL-LIKE RECEPTORS AND REGULATORY T CELLS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized with the generation of autoantibodies to different nucleus components. The generation and persistence of autoreactive B lymhocytes could result from the loss of immune tolerance, molecular mimicry, inappropriate clearance of apoptotic cells or changes in regulatory T cell (Treg) function. Infections have been known to trigger and/or aggravate SLE. Invading microorganisms are recognized by the innate immune system via Toll-like receptors (TLRs). TLR activation also modulates the function of Treg. We investigated the possible role of TLRs in SLE patients undergoing therapy with corticosteroids and chloroquine. Patients were analyzed at 3 time-points: before therapy, 3 weeks after the beginning of corticosteroid therapy, and again after 3 months, during which the corticosteroid dose was gradually lowered, and chloroquine introduced into the protocol. Also, we performed a two-year follow-up to examine the effect of therapy on the frequency of Foxp3-expressing Tregs in newly diagnosed SLE patient. Peripheral blood mononuclear cells were stained with fluorochrome-labeled monoclonal antibodies using three or four-color immunofluorescence staining protocol, and then analyzed on a flow cytometer. TLR2 expression on monocytes in patients after 3 weeks and 3 months of therapy was lower when compared with healthy controls. TLR9 expression on monocytes was lower in patients before therapy than in healthy controls, and on B cells after 3 weeks of therapy higher than in controls. The percentage of Tregs expressing Foxp3 increased to the levels observed in controls after three weeks of therapy but decreased again at two years, accompanied by slight deterioration of the patient’ s symptoms. Further experiments are under way to establish the importance of TLR and Treg as markers of disease activity and to investigate the possible therapeutic effects of steroids and other immunomodulatory drugs used in SLE.

Toll-like receptors; B cells; regulatory T cells; Foxp3

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