Dexamethasone inhibits the antigen presentation of dendritic cells in MHC class II pathway

Glucocorticoids (GC) are physiological inhibitors of inflammatory responses and are widely used as anti-inflammatory and immunosuppressive agents in t reatment of many autoimmune and allergic diseases. In the present study, we demonstrated that one of the mechanisms by which GC can suppress the immun e responses is to inhibit the differentiation and antigen presentation of d endritic cells (DC). DC were differentiated from murine bone marrow hematop oietic progenitor cells by culture with GM-CSF and IL-4 with or without dex amethasone (Dex). Our data showed that Dex, in a dose dependent manner, dow n-regulated surface expression of CD86, CD40, CD54 and MHC class II molecul es by DC, but the expression of MHC class I, CD80, CD95 and CD95L were not affected. In addition, Dex-treated DC showed an impaired function to activa te alloreactive T cells and to secrete IL-IP and IL-12p70. Moreover, Dex in hibited DC to present antigen by MHC class II pathway. However, the endocyt otic activity of DC was not affected. The inhibitory effect of Dex on the e xpression of costimulatory molecules and the antigen-presenting capacity of DC could be blocked by the addition of RU486, a potent steroid hormone ant agonist, suggesting the requirement of binding to cytosolic receptors in th e above-described action of Dex. Since DC have the unique property to prese nt antigen to responding naive T cells and are required in the induction of a primary response, the functional suppression of DC by Dex may be one of the mechanisms by which GC regulate immune responses in vivo. (C) 2001 Publ ished by Elsevier Science B.V. All rights reserved.