Genetic and cytological analyses reveal the recombination landscape of a partially differentiated plant sex chromosome in kiwifruit.

BACKGROUND: Angiosperm sex chromosomes, where present, are generally recently evolved. The key step in initiating the development of sex chromosomes from autosomes is the establishment of a sex-determining locus within a region of non-recombination. To better understand early sex chromosome evolution, it is important to determine the process by which recombination is suppressed around the sex determining genes. We have used the dioecious angiosperm kiwifruit Actinidia chinensis var. chinensis, which has an active-Y sex chromosome system, to study recombination rates around the sex locus, to better understand key events in the development of sex chromosomes. RESULTS: We have confirmed the sex-determining region (SDR) in A. chinensis var. chinensis, using a combination of high density genetic mapping and fluorescent in situ hybridisation (FISH) of Bacterial Artificial Chromosomes (BACs) linked to the sex markers onto pachytene chromosomes. The SDR is a subtelomeric non-recombining region adjacent to the nucleolar organiser region (NOR). A region of restricted recombination of around 6 Mbp in size in both male and female maps spans the SDR and covers around a third of chromosome 25. CONCLUSIONS: As recombination is suppressed over a similar region between X chromosomes and between and X and Y chromosomes, we propose that recombination is suppressed in this region because of the proximity of the NOR and the centromere, with both the NOR and centromere suppressing recombination, and this predates suppressed recombination due to differences between X and Y chromosomes. Such regions of suppressed recombination in the genome provide an opportunity for the evolution of sex chromosomes, if a sex-determining locus develops there or translocates into this region.

Aged human skin accumulates mast cells with altered functionality that localize to macrophages and vasoactive intestinal peptide-positive nerve fibres.

BACKGROUND: Skin health declines with age and this is partially attributed to immunosenescence. Mast cells (MCs) are innate immune cells that coordinate tissue immune responses integral to skin homeostasis and disease. OBJECTIVES: To understand how MCs contribute to human skin ageing, we investigated how intrinsic ageing impacts MC phenotype and MC relationships with other immune cells and skin structures. METHODS: In photoprotected skin biopsies from young (≤ 30 years) and aged (≥ 75 years) individuals, immunostaining and spatial morphometry were performed to identify changes in MC phenotype, number, distribution and interaction with the vasculature and nerve fibres. Quantitative polymerase chain reaction was used to measure changes in gene expression related to immune cell activity and neuropeptide signalling. RESULTS: Skin MCs, macrophages and CD8+ T cells increased in number in intrinsically aged vs. young skin by 40%, 44% and 90%, respectively (P < 0·05), while CD4+ T cells and neutrophils were unchanged. In aged skin, MCs were more numerous in the papillary dermis and showed a reduced incidence of degranulation (50% lower than in young, P < 0·01), a conserved tryptase-chymase phenotype and coexpression of granzyme B. In aged skin, MCs increased their association with macrophages (~ 48% vs. ~27%, P < 0·05) and nerve fibres (~29% vs. 16%, P < 0·001), while reducing their interactions with blood vessels (~34% vs. 45%, P < 0·001). Additionally, we observed modulation of gene expression of vasoactive intestinal peptide (VIP; increased) and substance P (decreased) with age; this was associated with an increased frequency of VIP+ nerve fibres (around three times higher in aged skin, P < 0·05), which were strongly associated with MCs (~19% in aged vs. 8% in young, P < 0·05). CONCLUSIONS: In photoprotected skin we observed an accumulation of MCs with increasing age. These MCs have both altered functionality and distribution within the skin, which supports a role for these cells in altered tissue homeostasis during ageing.

Impaired Langerhans cell migration in psoriasis is due to an altered keratinocyte phenotype induced by interleukin-17.

BACKGROUND: Psoriasis is a common skin condition driven by increased expression of interleukin (IL)-17. Langerhans cells (LCs) are epidermal dendritic cells that regulate cutaneous immune responses. Within the uninvolved skin of patients with psoriasis, LCs display impaired migration from the epidermis. OBJECTIVES: To investigate the role of keratinocytes (KCs) in the regulation of LC function and the response of KCs to IL-17. METHODS: KCs were cultured from the uninvolved skin of patients with psoriasis and healthy individuals with or without IL-17 treatment and the conditioned medium examined for its ability to alter LC function in an ex vivo human skin explant model. Furthermore, we examined the effect of IL-17 on LC mobilization in psoriasis by neutralizing IL-17 in the same skin explant model. RESULTS: Conditioned medium from psoriasis KCs inhibited LC migration in healthy skin. Moreover, conditioned medium from healthy KCs treated with IL-17 also inhibited healthy LC migration. Finally, neutralizing IL-17 in psoriasis skin resulted in enhanced LC migration. CONCLUSIONS: Collectively, these data suggest that an altered KC secretome, driven by increased expression of IL-17, is responsible for impaired LC migration in the uninvolved skin of patients with psoriasis.

N-Acyl ethanolamide and eicosanoid involvement in irritant dermatitis.

BACKGROUND: Sodium lauryl sulfate (SLS) and ultraviolet radiation (UVR) are two commonly encountered cutaneous inflammatory stimuli. Differing histopathological and clinical features implicate involvement of alternative inflammatory pathways; bioactive lipid mediators (eicosanoids, endocannabinoids and sphingolipids) are likely candidates for regulation of the divergent inflammatory responses. OBJECTIVES: To assess comprehensively bioactive lipid involvement in SLS- and UVR-induced inflammatory responses, to provide a better understanding of bioactive lipid mediator pathways in irritant inflammation. METHODS: Buttock skin from 10 healthy volunteers was treated with two minimal erythema doses of UVR (275-380 nm, peak 305 nm) or an SLS dose optimized for each individual, to produce a comparable, moderate erythema. Punch biopsies were taken 24 h postchallenge and from untreated skin, and separated into dermis and epidermis. Lipids [including 15 prostanoids, 15 hydroxy fatty acids (HFAs), nine endocannabinoids and related N-acyl ethanolamides (NAE), and 21 sphingolipids] were extracted and quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Increased epidermal NAE and HFA expression was observed in response to SLS but not UVR-induced low-level inflammation. Significant changes following SLS treatment included augmented levels of NAE, possessing proinflammatory and some reported anti-inflammatory properties, with 3·7-fold (P = 0·02) and threefold (P = 0·01) increased expression of palmitoyl and stearoyl ethanolamides, respectively, in addition to 1·9-fold (P = 0·02) increased expression of 12-hydroxyeicosatetraenoic acid. CONCLUSIONS: The differential bioactive lipid upregulation implicates their involvement in skin irritant responses, potentially reflecting roles in inflammatory cell recruitment and subsequent resolution of inflammation, giving scope for new treatment approaches to irritant dermatitis.