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Natural killer (NK) cells provide protection against infectious pathogens and cancer. For decades it has been appreciated that two major NK cell subsets (CD56bright and CD56dim) exist in humans and have distinct anatomical localization patterns, phenotypes, and functions in immunity. In light of this traditional NK cell dichotomy, it is now clear that the spectrum of human NK cell diversity is much...
In this issue of Immunity, Van Braeckel-Budimir et al. (2017) reveal that the pathogenic response of mice to a Plasmodium berghei infection is dominated by a Vβ8.1 T cell response. Mice lacking Vβ8.1 T cells fail to mount a pathogenic response, thus showing that the TCR locus can be an Immune response (Ir) gene.
Tissue-resident macrophages shape the development and homeostasis of the organs that they colonize. Yu et al. (2017) demonstrate that, unique to the lung, the instructive cytokine TGF-β collaborates with GM-CSF to induce the master transcription factor PPARγ to drive alveolar macrophage differentiation and maintenance early in life.
CD4+ T cells optimize the cytotoxic T cell (CTL) response in magnitude and quality, by unknown molecular mechanisms. We here present the transcriptomic changes in CTLs resulting from CD4+ T cell help after anti-cancer vaccination or virus infection. The gene expression signatures revealed that CD4+ T cell help during priming optimized CTLs in expression of cytotoxic effector molecules and many other...
Two recent Immunity papers provide new insight into efferocytosis by tissue-resident macrophages. Baratin et al. (2017) identify a resident macrophage population in the T cell zone of lymph nodes responsible for the silent uptake of vast numbers of apoptotic cells. Roberts et al. (2017) find that resident macrophages can be programmed by local tissue signals not to respond to the nucleic acid of apoptotic...
Pancreatic-islet inflammation contributes to the failure of β cell insulin secretion during obesity and type 2 diabetes. However, little is known about the nature and function of resident immune cells in this context or in homeostasis. Here we show that interleukin (IL)-33 was produced by islet mesenchymal cells and enhanced by a diabetes milieu (glucose, IL-1β, and palmitate). IL-33 promoted β cell...
Granulocyte-monocyte progenitors (GMPs) and monocyte-dendritic cell progenitors (MDPs) produce monocytes during homeostasis and in response to increased demand during infection. Both progenitor populations are thought to derive from common myeloid progenitors (CMPs), and a hierarchical relationship (CMP-GMP-MDP-monocyte) is presumed to underlie monocyte differentiation. Here, however, we demonstrate...
Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. Here we identified macrophage populations that continually engulf ACs in distinct tissues and found that these macrophages share characteristics compatible with immunologically silent clearance of ACs; such characteristics...
Understanding how broadly neutralizing antibodies (bnAbs) to HIV envelope (Env) develop during natural infection can help guide the rational design of an HIV vaccine. Here, we described a bnAb lineage targeting the Env V2 apex and the Ab-Env co-evolution that led to development of neutralization breadth. The lineage Abs bore an anionic heavy chain complementarity-determining region 3 (CDRH3) of 25...
Immune response (Ir) genes, originally proposed by Baruj Benacerraf to explain differential antigen-specific responses in animal models, have become synonymous with the major histocompatibility complex (MHC). We discovered a non-MHC-linked Ir gene in a T cell receptor (TCR) locus that was required for CD8+ T cell responses to the Plasmodium berghei GAP5040-48 epitope in mice expressing the MHC class...
Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental...
Alveolar macrophages (AMs) derive from fetal liver monocytes, which colonize the lung during embryonic development and give rise to fully mature AMs perinatally. AM differentiation requires granulocyte macrophage colony-stimulating factor (GM-CSF), but whether additional factors are involved in AM regulation is not known. Here we report that AMs, in contrast to most other tissue macrophages, were...
Innate and adaptive immune cells modulate heart failure pathogenesis during viral myocarditis, yet their identities and functions remain poorly defined. We utilized a combination of genetic fate mapping, parabiotic, transcriptional, and functional analyses and demonstrated that the heart contained two major conventional dendritic cell (cDC) subsets, CD103+ and CD11b+, which differentially relied on...
Chemoattractant-mediated recruitment of hematopoietic cells to sites of pathogen growth or tissue damage is critical to host defense and organ homeostasis. Chemotaxis is typically considered to rely on spatial sensing, with cells following concentration gradients as long as these are present. Utilizing a microfluidic approach, we found that stable gradients of intermediate chemokines (CCL19 and CXCL12)...
Although dysregulation of brain, immune, and gut physiology during pregnancy have each been implicated in neuropsychiatric disorders, whether and how these presumably distinct systems are linked to cause disease is unclear. Kim et al. (2017) and Shin Yim et al. (2017) identify a pathway to explain how these aspects of our physiology are deeply and inextricably connected.
Arterial remodeling participates pivotally in many diseases including arterial aneurysms. In this issue of Immunity, Da Ros et al. (2017) report that, in experimental aortic aneurysm formation, neutralization of interleukin-1β reduced arterial wall stiffness and hampered aneurysm development.
mTORC2 is a metabolic regulatory complex activated by PI3K. In this issue of Immunity, Kishore et al. (2017) demonstrate a specialized role for this complex in the migration of regulatory T (Treg) cells to sites of inflammation rather than their differentiation and survival.
Regulation of pancreatic insulin production is pivotal in the pathophysiology and treatment of diabetes. In this issue of Immunity, Dalmas et al. (2017) describe a type 2 immune circuit where pancreatic interleukin-33 (IL-33) promotes insulin secretion via the activity of islet-associated group 2 innate lymphoid cells (ILC2s).
T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumulation and control of chronic lymphocytic choriomeningitis virus (LCMV). We found...
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