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To better understand the stoichiometry of CD95L required to trigger apoptotic and nonapoptotic signals, we generated several CD95L concatemers from dimer to hexamer conjugated via a flexible link (GGGGS) 2 . These ligands reveal that although the hexameric structure is the best stoichiometry to trigger cell death, a dimer is sufficient to induce the apoptotic response in CD95-sensitive Jurkat cells. Interestingly, only trimeric and hexameric forms can implement a potent Ca 2+ response, suggesting that while CD95 aggregation controls the implementation of the apoptotic signal, both aggregation and conformation are required to implement the Ca 2+ pathway., (© 2023 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)

Fas ligand is increased in several immune-mediated diseases, including acute graft-versus-host disease, a donor cell-mediated disorder post-hematopoietic stem cell transplantation. In this disease, Fas ligand is involved in T-cell-mediated damage to host tissues. However, the role of its expression on donor non-T cells has, so far, never been addressed. Using a well-established CD4- and CD8-mediated graft-versus-host disease murine model, we found that precocious gut damage and mice mortality are increased with a graft of donor T- and B-depleted bone marrow cells devoid of Fas ligand as compared with their wild-type counterparts. Interestingly, serum levels of both soluble Fas ligand and IL-18 are drastically reduced in the recipients of Fas ligand-deficient grafts, indicating that soluble Fas ligand stems from donor bone marrow-derived cells. In addition, the correlation between the concentrations of these 2 cytokines suggests that IL-18 production arises through a soluble Fas ligand-driven mechanism. These data highlight the importance of Fas ligand-dependent production in IL-18 production and in mitigating acute graft-versus-host disease. Overall, our data reveal the functional duality of Fas ligand according to its source., (© The Author(s) 2023. Published by Oxford University Press on behalf of Society for Leukocyte Biology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We review the status of marine shellfish ecosystems formed primarily by bivalves in Australia, including: identifying ecosystem-forming species, assessing their historical and current extent, causes for decline and past and present management. Fourteen species of bivalves were identified as developing complex, three-dimensional reef or bed ecosystems in intertidal and subtidal areas across tropical, subtropical and temperate Australia. A dramatic decline in the extent and condition of Australia's two most common shellfish ecosystems, developed by Saccostrea glomerata and Ostrea angasi oysters, occurred during the mid-1800s to early 1900s in concurrence with extensive harvesting for food and lime production, ecosystem modification, disease outbreaks and a decline in water quality. Out of 118 historical locations containing O. angasi-developed ecosystems, only one location still contains the ecosystem whilst only six locations are known to still contain S. glomerata-developed ecosystems out of 60 historical locations. Ecosystems developed by the introduced oyster Crasostrea gigas are likely to be increasing in extent, whilst data on the remaining 11 ecosystem-forming species are limited, preventing a detailed assessment of their current ecosystem-forming status. Our analysis identifies that current knowledge on extent, physical characteristics, biodiversity and ecosystem services of Australian shellfish ecosystems is extremely limited. Despite the limited information on shellfish ecosystems, a number of restoration projects have recently been initiated across Australia and we propose a number of existing government policies and conservation mechanisms, if enacted, would readily serve to support the future conservation and recovery of Australia's shellfish ecosystems.