NK Cells in Autoimmune Disease

NK cells are not only found at sites of normal immune responses but have also been shown to accumulate in target organs of autoimmunity, for example, in the inflamed joints of RA (Dalbeth and Callan 2002; Tak et al. 1994), in brain lesions of MS (Traugott 1985), in psoriasis lesions (Cameron et al. 2002), and in the inflamed islets of Langerhans in IDDM (Miyazaki et al. 1985; Poirot et al. 2004; and our unpublished data). The presence of NK cells in target organs of autoimmunity, implying a role in disease at this site, is interesting in relation to findings reporting decreased NK cell numbers and impairment of NK cell function in peripheral blood in patients (Cameron et al. 2003; Yabuhara et al. 1996; and reviewed in Baxter and Smyth 2002; Flodstrom et al. 2002b; Grunebaum et al. 1989). Data from us and others show that rodents with diabetes also have compromised peripheral NK cells (Johansson et al. 2004; Poulton et al. 2001). It is not clear whether the reported alterations in blood NK cells reflect a secondary effect of disease or its treatment or are primary defects involved in the disease pathogenesis. Systemic induction of type 1 IFNs in mice rapidly depletes the spleen from NK cells and induces their migration into the liver (Salazar-Mather et al. 2002 and our observation). One possibility is that inflammatory cues alter the migratory pattern of NK cells and thus redistribute them from the circulation to target organs. This notion would suggest that low NK cell numbers in the blood may still be consistent with a role for NK cells elsewhere in the body.

The availability of mouse models for many human autoimmune diseases would appear to set a stage for analyzing the role for NK cells in these models. However, a general problem with studying NK cell function in vivo is that few markers or genes are expressed solely by NK cells. Many markers overlap with subsets of T cells or NKT cells (Raulet 2004), which makes NK cells difficult to target by knockout technology or by specific antibody depletion. Until now, only a few studies have been done in rodent models of autoimmune diseases in which the authors can confidently state that NK cells are the causative agent of the studied effect. Even so, the studies point toward both protective and disease-promoting effects of NK cells, depending on the disease model.

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