Zusammenfassung
Lymphotoxin-beta receptor (LTbetaR) signaling is known to play a key role in embryonic lymphoid organ formation as well as maintenance of lymphoid architecture. Activation of the LTbetaR is induced by either the heterotrimeric lymphotoxin-alpha(1)beta(2) (LTalpha(1)beta(2)) or the homotrimeric LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV gpD for herpes ...
Zusammenfassung
Lymphotoxin-beta receptor (LTbetaR) signaling is known to play a key role in embryonic lymphoid organ formation as well as maintenance of lymphoid architecture. Activation of the LTbetaR is induced by either the heterotrimeric lymphotoxin-alpha(1)beta(2) (LTalpha(1)beta(2)) or the homotrimeric LIGHT (homologous to lymphotoxins, exhibits inducible expression, and competes with HSV gpD for herpes virus entry mediator, a receptor expressed by T lymphocyte). Both ligands are expressed on activated lymphocytes. As mast cells reside in close proximity to activated T cells in some inflammatory tissues, we examined the expression of LTbetaR on bone marrow-derived mast cells and asked whether the LTbetaR-ligand interaction would allow communication between mast cells and activated T cells. We found that mast cells express LTbetaR at the mRNA as well as at the protein level. To investigate LTbetaR-specific mast cell activation, the LTbetaR on BMMC from either wild-type or LTbetaR-deficient mice was stimulated with recombinant mouse LIGHT or agonistic mAbs in the presence of ionomycin. LTbetaR-specific release of the cytokines IL-4, IL-6, TNF, and the chemokines macrophage inflammatory protein 2 and RANTES was detected. Moreover, coculture of mast cells with T cells expressing the LTbetaR ligands also entailed the release of these cytokines. Interference with a specific LTbetaR inhibitor resulted in significant suppression of mast cell cytokine release. These data clearly show that LTbetaR expressed on mast cells can transduce a costimulatory signal in T cell-dependent mast cell activation.
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