A comprehensive atlas of immunological differences between humans, mice and non-human primates, bioRxiv, 2019-03-12

Animal models are an integral part of the drug development and evaluation process. However, they are unsurprisingly imperfect reflections of humans, and the extent and nature of many immunological differences are unknown. With the rise of targeted and biological therapeutics, it is increasingly important that we understand the molecular differences in immunological behavior of humans and model organisms. Thus, we profiled a large number of healthy humans, along with three of the model organisms most similar to humans rhesus and cynomolgus macaques and African green monkeys; and the most widely used mammalian model mice. Using cross-species, universal phenotyping and signaling panels, we measured immune cell signaling responses to an array of 15 stimuli using CyTOF mass cytometry. We found numerous instances of different cellular phenotypes and immune signaling events occurring within and between species with likely effects on evaluation of therapeutics, and detail three examples (double-positive T cell frequency and signaling; granulocyte response to Bacillus anthracis antigen; and B cell subsets). We also explore the correlation of herpes simian B virus serostatus on the immune profile. The full dataset is available online at <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsflowrepository.org>httpsflowrepository.org<jatsext-link> (accession FR-FCM-Z2ZY) and <jatsext-link xmlnsxlink=httpwww.w3.org1999xlink ext-link-type=uri xlinkhref=httpsimmuneatlas.org>httpsimmuneatlas.org<jatsext-link>.

biorxiv immunology 100-200-users 2019

Conduit integrity is compromised during acute lymph node expansion, bioRxiv, 2019-01-24

Lymph nodes (LNs) work as filtering organs, constantly sampling peripheral cues. This is facilitated by the conduit network, a parenchymal tubular-like structure formed of bundles of aligned extracellular matrix (ECM) fibrils ensheathed by fibroblastic reticular cells (FRCs). LNs undergo 5-fold expansion with every adaptive immune response and yet these ECM-rich structures are not permanently damaged. Whether conduit integrity and filtering functions are affected during cycles of LN expansion and resolution is not known. Here we show that the conduit structure is disrupted during acute LN expansion but FRC-FRC contacts remain intact. In homeostasis, polarised FRCs adhere to the underlying substrate to deposit ECM ba-solaterally. ECM production by FRCs is regulated by the C-type lectin CLEC-2, expressed by dendritic cells (DCs), at transcriptional and secretory levels. Inflamed LNs maintain conduit size-exclusion, but flow becomes leaky, which allows soluble antigens to reach more antigen-presenting cells. We show how dynamic communication between peripheral tissues and LNs changes during immune responses, and describe a mechanism that enables LNs to prevent inflammation-induced fibrosis.Highlights<jatslist list-type=bullet><jatslist-item>FRCs use polarized microtubule networks to guide matrix deposition<jatslist-item><jatslist-item>CLEC-2PDPN controls matrix production at transcriptional and post-transcriptional levels<jatslist-item><jatslist-item>FRCs halt matrix production and decouple from conduits during acute LN expansion<jatslist-item><jatslist-item>Conduits leak soluble antigen during acute LN expansion<jatslist-item>

biorxiv immunology 100-200-users 2019

 

Created with the audiences framework by Jedidiah Carlson

Powered by Hugo