WSX-1 is the α subunit of the IL-27R complex expressed by T, B, NK/NKT cells, as well as macrophages and dendritic cells (DCs). Although it has been shown that IL-27 has both stimulatory and inhibitory effects on T cells, little is known on the role of IL-27/WSX-1 on DCs. LPS stimulation of splenic DCs in vivo resulted in prolonged CD80/CD86 expression on WSX-1-deficient DCs over wild-type DCs. Upon LPS stimulation in vitro, WSX-1-deficient DCs expressed Th1-promoting molecules higher than wild-type DCs. In an allogeneic MLR assay, WSX-1-deficient DCs were more potent than wild-type DCs in the induction of proliferation of and IFN-γ production by responder cell proliferation. When cocultured with purified NK cells, WSX-1-deficient DCs induced higher IFN-γ production and killing activity of NK cells than wild-type DCs. As such, Ag-pulsed WSX-1-deficient DCs induced Th1-biased strong immune responses over wild-type DCs when transferred in vivo. WSX-1-deficient DCs were hyperreactive to LPS stimulation as compared with wild-type DCs by cytokine production. IL-27 suppressed LPS-induced CD80/86 expression and cytokine production by DCs in vitro. Thus, our study demonstrated that IL-27/WSX-1 signaling potently down-regulates APC function and Th1-promoting function of DCs to modulate overall immune responses.
Interleukin (IL-) 27 is a member of IL-12 cytokine family with Th1-promoting and anti-inflammatory effects. IL-27 has been shown to facilitate tumor-specific cytotoxic T lymphocyte (CTL) induction against various tumors. However, IL-27 suppresses cytokine production of lymphocytes and antigen-presenting function of dendritic cells (DCs). To examine the in vivo role of IL-27 in generation of anti-tumor immunity, we examined IL-27-mediated antitumor-effects using WSX-1 (IL-27 receptor a chain)-deficient (WSX-1 2/2 ) mice. In WSX-1 2/2 mice inoculated with B16 melanoma cells, tumor growth was higher than in wild-type (WT) mice. Accordingly, tumor-specific CTL generation was lower in WSX-1 2/2 mice than in WT mice. CTL induction in WSX-1 2/2 mice was not restored by transfer of WT DCs pulsed with TRP2 peptide, indicating that IL-27 is directly required for generation of tumor-specific CTLs. However, when transferred into tumorbearing mice, WSX-1 2/2 DCs pulsed with TRP2 peptide was more potent than WT DCs in tumor growth inhibition and generation of CTLs, indicating suppressive effects of IL-27 on DC function. Finally, the combination of WT CD8 1 T cells and KO DCs is more potent in generation of antigen-specific CTLs than any other combinations. Expression of perforin gene and percentages of tumor-specific CD8 1 T cells were also the highest in the combination of WT CD81 T cells and WSX-1 2/2 DCs. It was thus revealed that IL-27 promotes CTL generation while suppressing DC function during generation of tumor immunity. The combination of WT T cells and IL-27 signal-defective DCs may have therapeutic potential against tumors.
There has been an argument as to whether early leaf abscission substantially affects larval mortality of leafminers because of leaf senescence. Recently, a study reported that leaf abscission considerably increased the mortality of a leafminer (Ectoedemia cerviparadisicola Sato, sp. nov.) associated with Quercus gilva (Blume) in Nara Park, central Japan, where sika deer (Cervus nippon (Temminck)) have been protected for 1,200 yr, because deer consumed many abscised leaves containing living larvae. The study, however, did not investigate the life history of the leafminer or survey the leaf-fall pattern of Q. gilva through the season, so that it failed to quantify larval mortality because of deer predation. To test whether deer have a substantial effect on larval mortality of this leafminer, we regularly collected abscised and nonabscised leaves of Q. gilva through the season, examining mines and larvae in those leaves. Over 90% of mined leaves abscised in the period of peak leaf fall, when almost all larvae had already emerged from mines to pupate. Most dead larvae in abscised leaves were judged to have already died at the time of abscission from their instars and body features. The proportion of living larvae in abscised leaves was estimated to be <1.8%. Thus, even when deer preyed upon all living larvae in abscised leaves, they would hardly contribute to the increase in larval mortality. These results indicate that the effect of leaf abscission on leafminer mortality via deer predation and other causes is limited. The leafminer was described as new to science in the Appendix.
Objective: Gene expression patterns differ in the two types of skeletal muscle fiber. The Wnt signaling pathway, which includes low-density lipoprotein receptor-related protein 6 (LRP6), has been associated with cell differentiation and glucose metabolism in skeletal muscles. We examined the relationships between muscle fiber types and LRP6 expression. Methods: Adenosine triphosphatase was assayed histochemically, and the levels of expression of LRP6 and myosin were analyzed immunohistochemically, in frozen sections of muscle fiber obtained from 16 muscle biopsy samples. The expression pattern of LRP6 in C2C12 cells was assayed by immunocytochemistry. Results: LRP6 was expressed only in type II fibers. Type IIc fibers showed variations in LRP6 expression. Expression of LRP6 was observed at the stage of myoblast differentiation. Conclusion: Antibody to LRP6 may be useful for identifying type II skeletal muscle fibers. LRP6 may influence glucose metabolism in type II fibers of human skeletal muscles.
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