Plasmodium infection induces phenotypic, clonal, and spatial diversity among differentiating CD4 T cells.

Naive CD4 T cells must differentiate in order to orchestrate immunity to Plasmodium, yet understanding of their emerging phenotypes, clonality, spatial distributions, and cellular interactions remains incomplete. Here, we observe that splenic polyclonal CD4 T cells differentiate toward T helper 1 (Th1) and T follicular helper (Tfh)-like states and exhibit rarer phenotypes not elicited among T cell receptor (TCR) transgenic counterparts. TCR clones present at higher frequencies exhibit Th1 skewing, suggesting that variation in major histocompatibility complex class II (MHC-II) interaction influences proliferation and Th1 differentiation.

The genome and population genomics of allopolyploid Coffea arabica reveal the diversification history of modern coffee cultivars.

Coffea arabica, an allotetraploid hybrid of Coffea eugenioides and Coffea canephora, is the source of approximately 60% of coffee products worldwide, and its cultivated accessions have undergone several population bottlenecks. We present chromosome-level assemblies of a di-haploid C. arabica accession and modern representatives of its diploid progenitors, C.

The transcription factor SpiB regulates the fibroblastic reticular cell network and CD8 T-cell responses in lymph nodes.

Fibroblastic reticular cells (FRCs) construct microanatomical niches that support lymph node (LN) homeostasis and coordination of immune responses. Transcription factors regulating the functionality of FRCs remain poorly understood. Here, we investigated the role of the transcription factor SpiB that is expressed in LN FRCs.

Divergent molecular networks program functionally distinct CD8 skin-resident memory T cells.

Skin-resident CD8 T cells include distinct interferon-γ-producing [tissue-resident memory T type 1 (T1)] and interleukin-17 (IL-17)-producing (T17) subsets that differentially contribute to immune responses. However, whether these populations use common mechanisms to establish tissue residence is unknown. In this work, we show that T1 and T17 cells navigate divergent trajectories to acquire tissue residency in the skin.

Fibroblastic reticular cells provide a supportive niche for lymph node-resident macrophages.

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models.

Splenic stromal niches in homeostasis and immunity.

The spleen is a gatekeeper of systemic immunity where immune responses against blood-borne pathogens are initiated and sustained. Non-haematopoietic stromal cells construct microanatomical niches in the spleen that make diverse contributions to physiological spleen functions and regulate the homeostasis of immune cells. Additional signals from spleen autonomic nerves also modify immune responses.

An optimized protocol for the isolation of rare stromal cell populations from the mouse spleen.

Lymphoid tissue stromal cells are important regulators of spleen homeostasis and immune responses. Here, we present an optimized protocol that describes the digestion and enrichment steps for the isolation and analysis of rare populations of stromal cells, including fibroblastic reticular cells, perivascular cells, and glial cells found in the spleen. This protocol is suitable for subsequent analysis of spleen stromal cells by flow cytometry or single-cell RNA sequencing and to analyze different disease models.

Corneal tissue-resident memory T cells form a unique immune compartment at the ocular surface.

The eye is considered immune privileged such that immune responses are dampened to protect vision. As the most anterior compartment of the eye, the cornea is exposed to pathogens and can mount immune responses that recruit effector T cells. However, presence of immune memory in the cornea is not defined.

CD169 macrophages in lymph node and spleen critically depend on dual RANK and LTbetaR signaling.

CD169 macrophages reside in lymph node (LN) and spleen and play an important role in the immune defense against pathogens. As resident macrophages, they are responsive to environmental cues to shape their tissue-specific identity. We have previously shown that LN CD169 macrophages require RANKL for formation of their niche and their differentiation.

A diverse fibroblastic stromal cell landscape in the spleen directs tissue homeostasis and immunity.

The spleen is a compartmentalized organ that serves as a blood filter and safeguard of systemic immune surveillance. Labyrinthine networks of fibroblastic stromal cells construct complex niches within the white pulp and red pulp that are important for tissue homeostasis and immune activation. However, the identity and roles of the global splenic fibroblastic stromal cells in homeostasis and immune responses are poorly defined.

Low-dose IL-2 therapy invigorates CD8+ T cells for viral control in systemic lupus erythematosus.

Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 (Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections.

Discrete tissue microenvironments instruct diversity in resident memory T cell function and plasticity.

Tissue-resident memory T (T) cells are non-recirculating cells that exist throughout the body. Although T cells in various organs rely on common transcriptional networks to establish tissue residency, location-specific factors adapt these cells to their tissue of lodgment. Here we analyze T cell heterogeneity between organs and find that the different environments in which these cells differentiate dictate T cell function, durability and malleability.

Activity of the adrenomedullin system to personalise post-discharge diuretic treatment in acute heart failure.

Background: Quantifying the activity of the adrenomedullin system might help to monitor and guide treatment in acute heart failure (AHF) patients. The aims were to (1) identify AHF patients with marked benefit or harm from specific treatments at hospital discharge and (2) predict mortality by quantifying the adrenomedullin system activity.

Methods: This was a prospective multicentre study.

Adrenergic regulation of the vasculature impairs leukocyte interstitial migration and suppresses immune responses.

The sympathetic nervous system (SNS) controls various physiological functions via the neurotransmitter noradrenaline. Activation of the SNS in response to psychological or physical stress is frequently associated with weakened immunity. Here, we investigated how adrenoceptor signaling influences leukocyte behavior.

Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.

T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate. After viral infection, we demonstrated that CD8 effector T cell differentiation is associated with positioning at the lymph node periphery.

Systemic Inflammation Suppresses Lymphoid Tissue Remodeling and B Cell Immunity during Concomitant Local Infection.

Concurrent infection with multiple pathogens occurs frequently in individuals and can result in exacerbated infections and altered immunity. However, the impact of such coinfections on immune responses remains poorly understood. Here, we reveal that systemic infection results in an inflammation-induced suppression of local immunity.

Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review.

Aims: This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients.

Methods And Results: A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward.

Measurement of Azimuthal Anisotropy of Muons from Charm and Bottom Hadrons in pp Collisions at sqrt[s]=13 TeV with the ATLAS Detector.

The elliptic flow of muons from the decay of charm and bottom hadrons is measured in pp collisions at sqrt[s]=13  TeV using a data sample with an integrated luminosity of 150  pb^{-1} recorded by the ATLAS detector at the LHC. The muons from heavy-flavor decay are separated from light-hadron decay muons using momentum imbalance between the tracking and muon spectrometers. The heavy-flavor decay muons are further separated into those from charm decay and those from bottom decay using the distance-of-closest-approach to the collision vertex.

Search for Magnetic Monopoles and Stable High-Electric-Charge Objects in 13 Tev Proton-Proton Collisions with the ATLAS Detector.

A search for magnetic monopoles and high-electric-charge objects is presented using 34.4  fb^{-1} of 13 TeV pp collision data collected by the ATLAS detector at the LHC during 2015 and 2016. The considered signature is based upon high ionization in the transition radiation tracker of the inner detector associated with a pencil-shape energy deposit in the electromagnetic calorimeter.

Observation of Light-by-Light Scattering in Ultraperipheral Pb+Pb Collisions with the ATLAS Detector.

This Letter describes the observation of the light-by-light scattering process, γγ→γγ, in Pb+Pb collisions at sqrt[s_{NN}]=5.02  TeV. The analysis is conducted using a data sample corresponding to an integrated luminosity of 1.

Combination of Searches for Invisible Higgs Boson Decays with the ATLAS Experiment.

Dark matter particles, if sufficiently light, may be produced in decays of the Higgs boson. This Letter presents a statistical combination of searches for H→invisible decays where H is produced according to the standard model via vector boson fusion, Z(ℓℓ)H, and W/Z(had)H, all performed with the ATLAS detector using 36.1  fb^{-1} of pp collisions at a center-of-mass energy of sqrt[s]=13  TeV at the LHC.

Search for the Production of a Long-Lived Neutral Particle Decaying within the ATLAS Hadronic Calorimeter in Association with a Z Boson from pp Collisions at sqrt[s]=13 TeV.

This Letter presents a search for the production of a long-lived neutral particle (Z_{d}) decaying within the ATLAS hadronic calorimeter, in association with a standard model (SM) Z boson produced via an intermediate scalar boson, where Z→ℓ^{+}ℓ^{-} (ℓ=e, μ). The data used were collected by the ATLAS detector during 2015 and 2016 pp collisions with a center-of-mass energy of sqrt[s]=13  TeV at the Large Hadron Collider and correspond to an integrated luminosity of 36.1±0.

Stromal cell networks coordinate immune response generation and maintenance.

Secondary lymphoid organs (SLO), including the spleen and lymph nodes (LN) are a meeting place for immune cells to initiate adaptive immune responses. Lymphocytes constantly circulate between SLO through the blood and lymph in search of their cognate antigen and are activated within the organized microarchitecture of SLO. Lymphoid stromal cells (LSC) of mesenchymal and endothelial origin construct and support the microarchitecture of SLO by defining distinct compartments and providing signals that can either promote or inhibit immune responses.

Local proliferation maintains a stable pool of tissue-resident memory T cells after antiviral recall responses.

Although tissue-resident memory T cells (T cells) are critical in fighting infection, their fate after local pathogen re-encounter is unknown. Here we found that skin T cells engaged virus-infected cells, proliferated in situ in response to local antigen encounter and did not migrate out of the epidermis, where they exclusively reside. As a consequence, secondary T cells formed from pre-existing T cells, as well as from precursors recruited from the circulation.