Although Langerhans cell histiocytosis (LCH) was first described a century ago, the aetiology is still not understood. Recent studies on the role of cytokines, chemokines, immunological dysfunction, cell surface antigen expression, clonality and cell-cycle regulation have provided new insights into the pathogenesis of LCH. Much of the data from these studies points to the Langerhans cell (LC) being intrinsically abnormal in LCH. Studies have shown that there is a proliferation of clonal LCs in the lesions of LCH. Furthermore, these LCH cells not only have differences in cytoplasmic and surface markers compared to the normal LC but also show abnormalities in cytokine production and antigen presentation. The recent progress in LCH research has provoked much discussion on whether LCH is a reactive disease resulting from environmental triggers, or a neoplastic process (Arceci et al., 2002; Egeler et al., 2004; Nezelof and Basset, 2004). Unfortunately, there is as yet no clear answer.

Continuing progress in the field of dendritic cell (DC) biology has allowed us to gain an increased understanding of the phenotype and function of LCH cells and their interaction with their microenvironment and hence the pathophysiology of this disease. Conversely, LCH, as an in vivo example of a DC abnormality, may serve as a ‘lesson’ to DC biologists (Laman et al., 2003). This chapter summarises some of the most recent studies investigating the immunological basis of LCH.