The functions of cutaneous DCs are modulated by keratinocytederived proinflammatory cytokines . The role of the different skin DC subsets in CHS is a matter of active debate . In addition, dermal DCs, including Langerin + dermal DCs, may also play an important role in CHS . Mast cells are a candidate DC modulator since they express and release a wide variety of intermediaries, such as histamine, tumor necrosis factor -a and lipid mediators. It has been reported that activated human cord blood-derived MCs induce DC maturation in vitro , that IgE-stimulated MC-derived histamine induces murine LC migration in vivo , and that MCderived TNF-a promotes cutaneous murine DC migration in vivo in an IgE-independent manner . On the other hand, prostaglandin D2 produced by MCs in response to allergens , inhibits LC migration . Therefore, MCs might have bidirectional effects on DC activity in a Fingolimod context-dependent manner and the question of the mechanisms by which DCs are modulated by MCs is an important issue to pursue. While MCs have been assumed to play an important role in CHS, their role is controversial. Previous ABT-263 customer reviews studies have demonstrated that MC-deficient Kit W/Wv mice show attenuated CHS responses, meanwhile, other studies have shown that CHS was not impaired in KitW/Wv mice . Although some studies indicated that the discrepancy in W/Wv mice might be due to the difference in hapten dose, the detailed mechanism is still unclear. Kit W/Wv mice and KitW-sh/KitW-sh mice have an inversion mutation in the Kit gene , and therefore, these mice also lack melanocytes and hematopoietic stem cells, which are known to modulate immune responses . In addition, since MCs are congenitally absent, it is possible that compensatory mechanisms may exist that modulates immune system functions. Therefore, it is important to re-evaluate the roles of MCs using mice in which MCs can be conditionally and specifically depleted. Recently, we have demonstrated that MCs and basophils use specific enhancer elements, intronic enhancer and a 39 4kb fragment that contains 39UTR and HS4 elements, to regulate Il4 gene expression, respectively . Taking advantage of this system, we have generated mice that contain human diphtheria toxin receptor under the control of IE. Therefore, mast cell-specific enhancer-mediated Toxin Receptor-mediated Conditional cell Knock out systems were designated as Mas- TRECK transgenic mice. In these mice, both MCs and basophils are conditionally depleted by diphtheria toxin treatment. Since basophils recover much faster than MCs , there exist a period of specific MC depletion. Taking advantage of the system, we have herein demonstrated that activated DCs induce MC activation, which triggers the migration and maturation of DCs via cell-cell contact.