Our skin is one of our major defences against disease, providing a barrier to pathogens and a home to epidermal Langerhans cells (LCs) and dermal dendritic cells (DCs). These professional antigen-presenting cells alert the immune system to invading pathogens by taking antigens from the skin to nearby lymph nodes, a journey that is hindered by intervening collagen-dense tissues. Mario Colombo and colleagues now report that SPARC (secreted protein, acidic and rich in cysteine), a matricellular protein that regulates collagen deposition in tissue stroma, modulates LC and DC migration in vivo (see p. 3685). The authors show first that the migration of these cells in SPARC-null mice is faster than in wild-type mice. Experiments in chimeric mice demonstrate that this increased migration is due to the host environment and that the lack of SPARC accelerates contact- and delayed-type hypersensitivity and T-cell priming. Thus, stromal SPARC expression, by determining the tightness of the extracellular matrix, influences the migration of LCs and DCs and hence the speed at which the immune system responds to invading pathogens.