Mast cells (MC) are bone marrow derived granulated cells which mature and reside within the connective tissue. MC can release a variety of preformed mediators such as histamine, proteases, cytokines, growth factors and proteoglycans by degranulation. 1 In inflammation, activated MC orchestrate the infiltration of leucocytes2 3 and present antigen to lymphocytes. 4 MC directly activate fibroblasts via gap junctions5 and coculture of MC with fibroblasts in vitro stimulates collagen production and enhances collagen contraction. 6 MC also regulate the proliferation of neighbouring fibroblasts. This effect is dependent on heterotypic cell-to-cell contact and requires the release of interleukin (IL)-4 by MC. 7 MC have been implicated in systemic sclerosis (SSc) pathology based on their increased numbers and degranulation in skin. 8 We showed recently that MC are a main source of transforming growth factor-β, a major profibrotic mediator. 9 In order to describe and characterise the ultrastructural interaction among MC, fibroblasts and lymphocytes in SSc, we studied the dermis of SSc patients by transmission electron microscopy. We obtained dermal skin biopsies from the forearm of four diffuse and three limited SSc patients, all of them fulfilling the LeRoy and Medsger’s criteria for SSc10 and from three healthy individuals. Ethical approval and written consent were obtained from all patients. For transmission electron microscopy, skin biopsies were fixed in 2% glutaraldehyde and embedded in epoxy resin. Heterogenic vesicle density was used to define the activation status of MC. Cell-to-cell contact between MC and fibroblasts as well as MC degranulation was scored as absent (-), moderate (+), intermediate (++) or abundant (+++). We detected cell-to-cell contacts between activated MC and fibroblasts in samples from four SSc patients, notably those with severe and diffuse skin thickening (table 1). MC activation, but not degranulation, seemed necessary for cell-to-cell contact formation. One patient who underwent prior autologous haematopoietic stem cell transplantation had no direct

MC–fibroblast contacts or MC degranulation. Dermal MC from all three healthy individuals were in an unactivated status with homogenic vesicle coloration. Occasionally, their cytoplasmic extensions appeared in proximity to fibroblasts, but no direct cell-to-cell contact, for example, by gap junctions with fibroblasts or lymphocytes was observed. Conversely, cell contacts between MC and fibroblasts in the four SSc patients were characterised by abundant gap junctions