Lichen planus (LP) is a relatively common disorder of the stratified squamous epithelia, which is, in many ways, an enigma. This paper is the consensus outcome of a workshop held in Switzerland in 1995, involving a selection of clinicians and scientists with an interest in the condition and its management. The oral (OLP) eruptions usually have a distinct clinical morphology and characteristic distribution, but OLP may also present a confusing array of patterns and forms, and other disorders may clinically simulate OLP. Lesions may affect other mucosae and/or skin. Lichen planus is probably of multifactorial origin, sometimes induced by drugs or dental materials, often idiopathic, and with an immunopathogenesis involving T-cells in particular. The etiopathogenesis appears to be complex, with interactions between and among genetic, environmental, and lifestyle factors, but much has now been clarified about the mechanisms involved, and interesting new associations, such as with liver disease, have emerged. The management of lichen planus is still not totally satisfactory, and there is as yet no definitive treatment, but there have been advances in the control of the condition. There is no curative treatment available; immunomodulation, however, can control the condition. Based on the observed increased risk of malignant development, OLP patients should be offered regular follow-up examination from two to four times annually and asked to report any changes in their lesions and/or symptoms. Follow-up may be particularly important in patients with atrophic/ulcerative/erosive affections of the tongue, the gingiva, or the buccal mucosa. Much more research is required into the genetic and environmental aspects of lichen planus, into the premalignant potential, and into the possible associations with chronic liver, and other, disorders. More clinical studies are required into the possible efficacy of immunomodulatory drugs such as pentoxifylline and thalidomide.

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Complement is the canonical innate immune system involved in host defense and tissue repair with the clearance of cell debris. In contrast to the robust armory mounted against microbial nonselfpathogens, complement is selectively activated on altered self (i.e. apoptotic and necrotic cells) to instruct the safe demise by poorly characterized mechanisms. Our data shed new light on the role of complement C1q in sensing nucleic acids (NA) rapidly exposed on apoptotic Jurkat T cell membranes and in driving C3 opsonization but without the lytic membrane attack complex. DNA/RNasetreated apoptotic cells failed to activate complement. We found that several other apoptotic cell models, including senescent keratinocytes, ionophore-treated sperm cells, and CMK-derived platelets, stained for cleaved caspase 3 were rapidly losing the key complement regulator CD46. CD46 from nuclear and membrane stores was found to cluster into blebs and shed into microparticles together with NA, phosphatidylserine, C1q, and factor H. Classical and alternative pathways of complement were involved in the recognition of H 2 O 2 -treated necrotic cells. Membrane attack complex was detected on necrotic cells possibly as a result of CD46 and CD59 shedding into soluble forms. Our data highlight a novel and universal paradigm whereby the complement innate immune system is using two synergistic strategies with the recognition of altered self-NA and missing self-CD46 signals to instruct and tailor the efficient removal of apoptotic and necrotic cells in immunoprivileged sites.

Central nervous system (CNS) tissues contain cells (i.e. glia and neurons) that have innate immune functions. These cells express a range of receptors that are capable of detecting and clearing apoptotic cells and regulating inflammatory responses. Phagocytosis of apoptotic cells is a nonphlogistic (i.e. noninflammatory) process that provides immune regulation through anti-inflammatory cytokines andregulatory T cells. Neurons and glia express cellular death signals, including CD95Fas/CD95L, FasL, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and tumor necrosis factor receptor 1 (TNFR), through which they can trigger apoptosis in T cells and other infiltrating cells. Microglia, astrocytes, ependymal cells, and neurons express defense collagens and scavenger and phagocytic receptors that recognize apoptotic cells displaying apoptotic cell-associated molecular patterns, which serve as markers of "altered self." Glia also express pentraxins and complement proteins (C1q, C3b, and iC3b) that opsonize apoptotic cells, making them targets for the phagocytic receptors CR3 and CR4. Immunoregulatory molecules such as the complement regulator CD46 are lost from apoptotic cells and stimulate phagocytosis, whereas the expression of CD47 and CD200 is upregulated during apoptosis; this inhibits proinflammatory microglial cytokine expression, thereby reducing the severity of inflammation. This review outlines the cellular pathways used for the detection and phagocytosis of apoptotic cells in vitro and in experimental models of CNS inflammation.

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