Vitamin D(3) deficiency enhances allergen-induced lymphocyte responses in a mouse model of allergic airway disease.

There is debate as to whether vitamin D deficiency contributes towards the extent of the asthma epidemic. In this study, using a mouse model, we determined whether vitamin D deficiency in utero and during early life modulated the severity of asthma. Using dietary restriction, vitamin D(3) -replete and vitamin D(3) -deficient colonies of BALB/c mice were established. Utilizing the allergic airway disease model of asthma with the experimental allergen ovalbumin (OVA), we examined asthma-like responses 24 h after airway challenge with OVA in adult offspring born to vitamin D(3) -replete and vitamin D(3) -deficient mothers. The ability of airway-draining lymph node cells to proliferate and secrete cytokines in response to OVA ex vivo was significantly enhanced by vitamin D(3) deficiency. However, other aspects of allergic disease, including the numbers and proportions of inflammatory cells and cytokines in the lungs and the quantity of OVA-specific IgE in serum, were not modified. These results suggest that vitamin D(3) deficiency modulates the capacity of lymphocytes to respond to allergens.

Differences in control by UV radiation of inflammatory airways disease in naïve and allergen pre-sensitised mice.

Exposure of skin to UV radiation (UVR) prior to allergen exposure can inhibit inflammatory airways disease in mice by reducing effector CD4+ T cells in both the trachea and the airway draining lymph nodes. This study analysed the immunomodulatory properties of UVR delivered to naïve versus allergen pre-sensitised mice. In a model of inflammatory airways disease, BALB/c mice were sensitised by peritoneal injection of the allergen, ovalbumin (OVA) (20 µg/mouse), in the adjuvant, alum (4 mg/mouse), on days 0 and 14. On day 21, the mice were exposed to aerosolised OVA and 24 h later, proliferative responses by the cells in the airway draining lymph nodes were examined. UVR (8 kJ m(-2)) was administered 3 days prior to first OVA sensitisation (day -3), or OVA aerosol challenge (day 18). UVR before sensitisation reduced immune responses associated with expression of allergic airways disease; seven days after first OVA sensitisation, regulation of OVA-induced proliferation in vitro but not in vivo by CD4+CD25+ cells from UV-irradiated mice was detected. UVR administered to pre-sensitised mice regulated allergen responsiveness by cells from the airway draining lymph nodes only with a sensitisation protocol involving allergen and adjuvant at 5% strength of the original dose (1 µg OVA in 0.2 mg alum/mouse). These results suggest that UVR may modulate allergic airways disease by two mechanisms. The first, and more potent, is by reducing effector cells in respiratory tissues and requires UV delivery prior to sensitisation. The second, associated with administration to pre-sensitised mice, is weaker and is detected when the mice are sensitised with lower levels of allergen and adjuvant.

UV exposure and protection against allergic airways disease.

Asthma is a chronic inflammatory disease of the small and large conducting airway mucosa characterised by Th2 cell immunity. Allergen-specific IgE levels control the immediate response whilst the interplay between airway mucosal antigen presenting cells, Th2 effector cells and CD4+CD25+ regulatory T cells control the late phase, cell-mediated response. Using two experimental systems in mice with ovalbumin and papain, respectively, as the allergens, UV irradiation of skin prior to allergen sensitisation reduced the expression of allergic airways disease, particularly the late phase response. In this review, the reduced Th2-driven, asthma-like responses in respiratory tissues of UV-irradiated mice are detailed. Possible mechanisms of UV regulation are debated. The potential beneficial effects of UV irradiation of skin in controlling allergic airways disease are discussed. This review gives some scientific understanding to century-old anecdotal reports that beach and mountain resort holidays associated with increased UV exposure are beneficial in asthma treatment.

Pea LATE BLOOMER1 is a GIGANTEA ortholog with roles in photoperiodic flowering, deetiolation, and transcriptional regulation of circadian clock gene homologs.

Genes controlling the transition to flowering have been studied in several species, including Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa), but have not yet received much attention in legumes. Here, we describe a new allelic series of late-flowering, photoperiod-insensitive mutants in the pea (Pisum sativum) LATE BLOOMER1 (LATE1) gene and show that LATE1 is an ortholog of Arabidopsis GIGANTEA. Mutants display defects in phytochrome B-dependent deetiolation under red light and in the diurnal regulation of pea homologs of several Arabidopsis circadian clock genes, including TIMING OF CAB1, EARLY FLOWERING4, and CIRCADIAN CLOCK ASSOCIATED1/LATE ELONGATED HYPOCOTYL. LATE1 itself shows strongly rhythmic expression with a small but distinct acute peak following dark-to-light transfer. Mutations in LATE1 prevent the induction of a FLOWERING LOCUS T (FT) homolog FTL in long days but cause only minor alteration to the rhythmic expression pattern of the only known group Ia CONSTANS homolog COLa. The late-flowering phenotype of late1 mutants can be completely rescued by grafting to the wild type, but this rescue is not associated with a significant increase in FTL transcript level in shoot apices. Genetic interactions of late1 with the photoperiod-insensitive, early-flowering sterile nodes (sn) mutant and impairment of the LATE1 diurnal expression rhythm in sn plants suggest that SN may also affect the circadian clock. These results show that several functions of Arabidopsis GIGANTEA are conserved in its pea ortholog and demonstrate that genetic pathways for photoperiodic flowering are likely to be conserved between these two species. They also suggest that in addition to its role in the floral transition, LATE1 also acts throughout reproductive development.