| First Author | Kobayashi T | Year | 2017 |
| Journal | Int Immunol | Volume | 29 |
| Issue | 12 | Pages | 551-566 |
| PubMed ID | 29155995 | Mgi Jnum | J:258080 |
| Mgi Id | MGI:6112943 | Doi | 10.1093/intimm/dxx063 |
| Citation | Kobayashi T, et al. (2017) Lysosome biogenesis regulated by the amino-acid transporter SLC15A4 is critical for functional integrity of mast cells. Int Immunol 29(12):551-566 |
| abstractText | Mast cells possess specialized lysosomes, so-called secretory granules, which play a key role not only in allergic responses but also in various immune disorders. The molecular mechanisms that control secretory-granule formation are not fully understood. Solute carrier family member 15A4 (SLC15A4) is a lysosome-resident amino-acid/oligopeptide transporter that is preferentially expressed in hematopoietic lineage cells. Here, we demonstrated that SLC15A4 is required for mast-cell secretory-granule homeostasis, and limits mast-cell functions and inflammatory responses by controlling the mTORC1-TFEB signaling axis. In mouse Slc15a4-/- mast cells, diminished mTORC1 activity increased the expression and nuclear translocation of TFEB, a transcription factor, which caused secretory granules to degranulate more potently. This alteration of TFEB function in mast cells strongly affected the FcepsilonRI-mediated responses and IL-33-triggered inflammatory responses both in vitro and in vivo. Our results reveal a close relationship between SLC15A4 and secretory-granule biogenesis that is critical for the functional integrity of mast cells. |
