Analysis of functions of cutaneous mast cells using murine fetal skin-derived cultured mast cells

点击翻译按钮获取中文摘要

Toll-like receptors (TLR) mediate innate immune responses by their binding to viral and bacterial products. Recent studies revealed that TLR3 binds to viral double-stranded RNA and that TLR9 binds to CpG motifs, consensus oligodeoxynucleotide sequences specific to bacteria and viruses. This study aimed to determine whether mast cells in skin express TLR3 and TLR9. First we identified mRNA expression of TLR3 and TLR9 in murine fetal skin-derived cultured mast cells (FSMC) that closely resemble cutaneous mast cells. The expression levels of both TLR3 and TLR9 in FSMC were several-fold greater than those in bone marrow-derived cultured mast cells (BMMC) that represent immature (or mucosal) mast cells. Furthermore, FSMC phosphorylated IkBa and secreted cytokines including TNF-a and IL-6 and chemokines including MIP-1a and MIP-2 in response to poly (I:C) (synthetic ligand of TLR3) and CpG oligodeoxynucleotides (but not to randomized oligodeoxynucleotides) to much greater extents than BMMC did. These data assure expression of functional TLR3 and TLR9 on FSMC, and also suggest that their expression may be differentially regulated depending on differentiation of mast cells. Interestingly, unlike stimulation of mast cells through FceRI, stimulation through TLR3 and TLR9 did not cause degranulation and did not induce production of IL-13. Thus skin-associated mast cells express TLR3 and TLR9, recognize pathogen-specific nucleotides, and release proinflammatory cytokines. The absence of IL-13 may be advantageous for the following Th1 responses. Our results suggest novel roles of cutaneous mast cells in innate immunity distinct from their roles in IgE- and Th2-mediated allergic responses.