CD55 deposited on synovial collagen fibers protects from immune complex-mediated arthritis

IntroductionCD55, a glycosylphosphatidylinositol-anchored, complement-regulating protein (decay-accelerating factor), is expressed by fibroblast-like synoviocytes (FLS) with high local abundance in the intimal lining layer. We here explored the basis and consequences of this uncommon presence.MethodsSynovial tissue, primary FLS cultures, and three-dimensional FLS micromasses were analyzed. CD55 expression was assessed by quantitative polymerase chain reaction (PCR), in situ hybridization, flow cytometry, and immunohistochemistry. Reticular fibers were visualized by Gomori staining and colocalization of CD55 with extracellular matrix (ECM) proteins by confocal microscopy. Membrane-bound CD55 was released from synovial tissue with phospholipase C. Functional consequences of CD55 expression were studied in the K/BxN serum transfer model of arthritis using mice that in addition to CD55 also lack FcγRIIB (CD32), increasing susceptibility for immune complex-mediated pathology.ResultsAbundant CD55 expression seen in FLS of the intimal lining layer was associated with linearly oriented reticular fibers and was resistant to phospholipase C treatment. Expression of CD55 colocalized with collagen type I and III as well as with complement C3. A comparable distribution of CD55 was established in three-dimensional micromasses after ≥3 weeks of culture together with the ECM. CD55 deficiency did not enhance K/BxN serum-induced arthritis, but further exaggerated disease activity in Fcgr2b^−/− mice.ConclusionsCD55 is produced by FLS and deposited on the local collagen fiber meshwork, where it protects the synovial tissue against immune complex-mediated arthritis.

Electronic supplementary material

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Ecological and Conservation Significance of Herpesvirus Infection in Neotropical Bats

EcoHealth - Bats are the second most diverse order of mammals and key species for ecosystem functioning, providing a wide range of ecosystem services, from pest control to seed dispersal....     

Spatial distribution and prediction of seed production by Eucalyptus microcarpa in a fragmented landscape

Woodlands worldwide have been greatly modified by clearing for agriculture, and their conservation and restoration requires understanding of tree recruitment processes. Seed production is one possible point of recruitment failure, and one that the spatial arrangement of trees may affect. We sampled 118 Eucalyptus microcarpa (Myrtaceae) trees to compare and analyse the determinants of seed production in this dominant tree of modified, fragmented temperate grassy woodlands, which extend over much of southeastern Australia. Fecundity was estimated as the seed crop measured on leaf mass and whole tree bases and was compared between categories of tree configuration. We also modelled fecundity using boosted regression trees, a new and flexible tool. Fecundity on a leaf mass basis was predominantly influenced by environmental factors (topographic ‘wetness’, slope, soil type), rather than by local tree density and configuration. Fewer seed per unit leaf mass were produced on flat and topographically wet sites, reflecting poor tolerance of waterlogging by E. microcarpa. By contrast, whole tree fecundity was little influenced by environmental factors. Local tree density and configuration did influence whole tree fecundity, which was high in solitary and woodland‐spaced trees and reduced under high local density. We found little evidence for reduced fecundity of E. microcarpa in solitary trees. This points to the importance of scattered trees as sources of seed for tree recruitment and for natural regeneration of landscape level tree cover. Considerable uncertainty remains in modelled seed supply, and may be reduced with sampling across multiple years and greater environmental and spatial domains.