People & Ideas
Germinal centers can be induced by T-independent antigens. Liu et al. show that, surprisingly, these germinal centers can produce long-lived memory B cell and plasma cell output.
VEGF receptors are essential regulators of blood and lymphatic vessel growth and maintenance. Karaman et al. used single and compound mutants of VEGFR1, 2, and 3 to reveal organ-specific roles for each of these receptors and interactions between them.
Cross-talk between the nervous system and the immune system is important in normal physiology and disease. This review discusses how neural signals regulate leukocyte migration around the body and within tissues and contributions by diverse neural signals to effective immune responses.
The vasculature of the meninges contains fenestrated endothelium conferring vulnerability to invasion by circulating microbes, often arising from the gut. Here, we discuss how close links between intestinal and meningeal immunity enable central nervous system defense against blood-borne invaders.
Brief Definitive Reports
T-independent antigens are known to induce transient germinal center formation. Liu et al. show that these germinal centers output memory B cells and plasma cells and condition their persistence.
Here, the authors report the first description of two infants with PIK3CA-related overgrowth spectrum treated by alpelisib. Patients were monitored with pharmacokinetics. Alpelisib was associated with clinical, biological, and radiological improvements.
Tau present in the extracellular fluids has a critical role in the pathogenesis of tauopathies. The authors describe that glymphatic clearance of extracellular tau impacts tau accumulation and neurodegeneration. The study implicates glymphatic system in the pathophysiology of tauopathies.
Molecular architecture determines brain delivery of a transferrin receptor–targeted lysosomal enzyme
Brain delivery, biodistribution, and pharmacodynamics of a lysosomal enzyme fused to a moderate-affinity transferrin receptor–directed blood–brain barrier enzyme transport vehicle are superior to a traditional high-affinity anti-TfR monoclonal antibody fusion.
Technical Advances and Resources
Single-cell immune profiling reveals functional diversity of T cells in tuberculous pleural effusion
Cai et al. describe their finding of cellular diversity in tuberculous pleural effusion (TPE). They establish a link between clonal expansion and lineage plasticity of T cells and reveal the involvement of granzyme K–expressing CD8 T cells in TPE pathogenesis.
Specific populations of immune cells in the adult develop from the embryonic yolk sac, independent of hematopoietic stem cells. Using the human pluripotent stem cell model, this study has mapped human yolk sac hematopoiesis, providing access to these developmentally restricted progenitors.
Using VEGF receptor deletions in mice, the authors show that VEGFR1 and VEGFR3 can support vessel maintenance in the absence of VEGFR2 in an organ-specific manner in postnatal and adult mice.
Single-cell transcriptomic analysis shows that macrophages in mucosa and muscularis propria of human colon are very heterogeneous and that their functional properties are closely related to their anatomic position. The study indicates that distinct differentiation pathways are controlled by extensive interactions with tissue-resident cells.
Epitope convergence of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a viremic controller
This study identifies a trio of broadly HIV-1 neutralizing IgA and IgG antibody lineages in a HIV-1 viremic controller that all target a unique viral site of vulnerability.
Disruption of thymic central tolerance by infection with murine roseolovirus induces autoimmune gastritis
Bigley et al. show that neonatal murine roseolovirus infection disrupts central tolerance. Autoimmunity arises later, in the absence of ongoing infection. This study provides evidence for a new mechanism by which viruses induce autoimmunity at a time remote from initial infection.
Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function
Dyck et al. describe suppressive effects of obesity on CD8 T cells in mouse cancer models and human endometrial cancer. Immunotherapy using anti–PD-1 is effective in obesity and partially restores CD8 T cell function and metabolism in mice.
Liu et al. demonstrate the regulation of ILC2 by Ang II–AT1 signaling during the allergen challenge. Bone marrow chimera, deletion or pharmacological inhibition of AT1a, and ILC2 transfer into NCG mice collectively indicate that targeting lung RAS alleviates airway inflammation.
TIRAP drives myelosuppression through an Ifnγ–Hmgb1 axis that disrupts the endothelial niche in mice
The molecular drivers of myelodysplastic syndromes are not fully elucidated. We identify a novel, noncanonical role of TIRAP in myelopoiesis through the regulation of bone marrow endothelium via an Ifnγ–Hmgb1 axis. These findings reveal novel mechanisms of Ifnγ function in the bone marrow microenvironment and provide insight into the pathophysiology of preleukemic syndromes.
Microglia modulate cerebral blood flow (CBF) through complex purinergic actions, which are mediated by dynamic, P2Y12 receptor-driven interactions with the vasculature. Microglial actions are partially independent of nitric oxide. Microglial dysfunction leads to impaired CBF response during neurovascular coupling, hypercapnia-induced vasodilation and cerebral hypoperfusion.
Correction: Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function