Dexamethasone and other steroids used for treating psoriatic skin inflammation probably act in part by inducing I-kB, thus preventing NF-kB from reaching the nucleus and trans-activating its many target genes, including those involved in T cell-dependent inflammation. Zollner and colleagues now propose a different means to this same end: Since the proteasome is responsible for the regulated turnover of I-kB, proteasome inhibitors might also alleviate psoriasis by blocking NF-kB activation. Indeed, such inhibitors have already been used successfully in animal models of rheumatoid arthritis and multiple sclerosis, conditions that (like psoriasis) are thought to result from T cell exposure to bacterial antigens. Working with human psoriatic skin tissue engrafted onto mice, Zollner et al. confirm that a known bacterial superantigen can provoke psoriatic lesions. They find that proteasome inhibition prevents NF-kB activation in cultured T cells and that it blocks expression of adhesive surface molecules required for T cell homing. In engrafted mice, the inhibitor prevents psoriasis as efficiently as dexamethasone does. These different agents, which can each increase I-kB levels, presumably both silence NF-kB target genes in vivo. In addition, however, proteasome inhibitors might exert other beneficial effects, since they undoubtedly stabilizes a variety of short-lived proteins, some of which could block disease progression by other mechanisms.