皮膚型マスト細胞モデルの確立とその解析

抄録

  Mast cells originate from hematopoietic stem cells and undergo terminal differentiation in the tissues, in which they are ultimately resident. Heterogeneity of tissue mast cells is, therefore, one of the key concepts for a better understanding of immune modulation by mast cells. Since no appropriate culture model has been developed for tissue mature mast cells, it was difficult to investigate the tissue-specific functions of mast cells. We established a novel cutaneous mast cell model by modifying the previously reported co-culture system with fibroblastic cell line. This model shares many characteristics with cutaneous mast cells, such as staining properties, sensitivity to cationic secretagogues, and higher levels of granule histamine and proteases. We extracted the candidate genes that should regulate differentiation and functions of mast cells by analyses of the gene expression profiles during the co-culture period. We further investigated the functions of cluster of differentiation 44 (CD44), which is the primary receptor of hyaluronan in mast cells, since CD44 was up-regulated during the co-culture period. Fluorescence study revealed that mast cells expressing CD44 were bound to the extracellular matrix containing hyaluronan and lack of CD44 impaired proliferation of the co-cultured mast cells. In the CD44^−/− mice, the number of cutaneous mast cells was significantly decreased. Reconstitution analyses with the mast cell deficient strain revealed that CD44 expressed in mast cells should be required in the proliferation in the cutaneous tissues. In the next phase of mast cell research, it might become increasingly important to focus on the heterogeneity of tissue mast cells.