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Buckingham, L.

Publications and source records attributed to Buckingham, L..

3 recordsLinked to original sources

CD200R1 is required for the development of γδ 17 T cells

{gamma}{delta} T cells are enriched at barrier sites such as skin, gut and lung, where they protect against cancer and infections and promote healing. They detect diverse ligands in T cell receptor-dependent or independent manners, producing large quantities of pro-inflammatory cytokines. {gamma}{delta} T cells develop in foetal thymi in temporally controlled waves where, unlike {beta} T cells, many {gamma}{delta} T cells adopt their effector fate, becoming either IFN{gamma} or IL-17A-producers ({gamma}{delta}17 T cells). CD200R1 suppresses myeloid cell activity but has also been shown to promote innate lymphoid cell IL-17A production, enhancing psoriasis-like skin inflammation. {gamma}{delta}17 T cells are potent IL-17A producers in skin therefore, the effect of CD200R1 on IL-17A production by {gamma}{delta}17 T cells was investigated. CD200R1 was found to promote IL-17A production by {gamma}{delta} T cells by supporting the development of {gamma}{delta}17 T cells, enhancing IL-17-producing and ROR{gamma}t+ {gamma}{delta} T cell numbers in foetal thymic organ cultures. To fulfil this role, CD200R1 acts either directly on developing {gamma}{delta} T cells, or indirectly on thymic stromal cells. This identifies CD200R1 as a critical novel regulator of {gamma}{delta}17 T cell development in early life, a key process for ensuring immunity, particularly at barrier sites.

immunology↗

Temporal and spatial variability in availability bias has consequences for marine bird abundance estimates during the non-breeding season

O_LITo effectively monitor how marine ecosystems are being reshaped by anthropogenic pressures, we require understanding of species abundances and distributions. Due to their socio-economic and ecological value, predatory species are often at the forefront of survey efforts. However, survey data are only valuable if they can reliably be converted into estimates of underlying distributions. C_LIO_LIWe consider at-sea surveys of marine predators that often inform ecological impact assessments of offshore windfarms. These surveys are subject to a form of detection bias called availability bias whereby individuals which are submerged below the surface are consequently unavailable for detection. Although correction factors are commonly used in these surveys, they are currently based on limited data that may not be species-, time-, or area-specific. Here, we use time-depth-recorder data to investigate variation in marine bird availability bias. C_LIO_LIWe found that the proportion of diving marine birds submerged below the sea surface during daylight hours, and therefore unavailable to be counted during surveys, varied by species, month, and area. For three of our focal species wintering around northwest Europe (Atlantic puffin, common guillemot, razorbill) our results were different to comparable values previously used to correct for the availability bias, whereas no correction factors are regularly used for the fourth species (red-throated diver). We now present availability bias correction factors that are species- and month-specific to the areas the study populations use during their non-breeding seasons: the North Sea, the north and west coasts of the UK, the Baltic Sea, and Icelandic coastal waters. C_LIO_LISynthesis and applications: Variation in the proportion of daylight hours that marine birds spent submerged lead to differences in availability bias correction factors, thereby impacting estimations of their abundances. We encourage use of correction factors that use data from the species, marine area, and month during which surveys are conducted to provide more accurate abundance estimates. Using more relevant correction factors will result in increasingly accurate abundance and distribution estimates of diving marine birds, with relevance for a range of applications including planning for offshore windfarm developments, the designation and monitoring of protected areas, and understanding environmental change. C_LI

ecology↗

CD200R1 promotes IL-17 production by ILC3s, by enhancing STAT3 activation

Psoriasis is a common chronic inflammatory skin disease with no cure. It is driven by the IL-23/IL-17A axis and TH17 cells but, recently group 3 innate lymphoid cells (ILC3s) have also been implicated. However, the development, and factors regulating the activity of ILC3s remain incompletely understood. Immune regulatory pathways are particularly important at barrier sites such as the skin, gut and lung, which are exposed to environmental substances and microbes. CD200R1 is an immune regulatory cell surface receptor which inhibits proinflammatory cytokine production in myeloid cells. CD200R1 is also highly expressed on ILCs, where its function remains largely unexplored. We previously observed reduced CD200R1 signalling in psoriasis skin, suggesting that dysregulation may promote disease. Here we show that contrary to this, psoriasis models are less severe in CD200R1-deficient mice due to reduced IL-17 production. Here we uncover a key cell-intrinsic role for CD200R1 in promoting IL-23-driven IL-17A production by ILC3s, by promoting STAT3 activation. CD200R1 is expressed on ILC precursors and is particularly high on neonatal ILC3s, suggesting CD200R1 may function during ILC development. Therefore, CD200R1 is required on ILC3s, potentially during their development, to promote IL-23-stimulated STAT3 activation triggering optimal IL-17 production.

immunology↗