Misbehaving macrophages in the pathogenesis of psoriasis.
Psoriasis is a chronic inflammatory skin disease unique to humans. In this issue of the JCI, 2 studies of very different mouse models of psoriasis both report that macrophages play a key role in inducing psoriasis-like skin disease. Psoriasis is clearly a polygenic, inherited disease of uncontrolled cutaneous inflammation. The debate that currently rages in the field is whether psoriasis is a disease of autoreactive T cells or whether it reflects an intrinsic defect within the skin--or both. However, these questions have proven difficult to dissect using molecular genetic tools. In the current studies, the authors have used 2 different animal models to address the role of macrophages in disease pathogenesis: Wang et al. use a mouse model in which inflammation is T cell dependent, whereas the model used by Stratis et al. is T cell independent (see the related articles beginning on pages 2105 and 2094, respectively). Strikingly, both groups report an important contribution by macrophages, implying that macrophages can contribute to both epithelial-based and T cell-mediated pathways of inflammation.
Clark
Rachael A
RA
Harvard Skin Disease Research Center and Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Kupper
Thomas S
TS
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000503:physiopathology; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D051379:Mice; D011565:Psoriasis / Q000209:etiology / Q000276:immunology / Q000503:physiopathology*