Change and flow
The water you touch in a river is the last of that which has passed and the first of that which is coming. Thus it is with time present.—Leonardo da Vinci
Immunity
State-specific enhancer landscapes govern microglial plasticity
Microglia adopt diverse states throughout life. Whether these represent fixed lineages or reversible plasticity remains unclear. Hamagami and Kapadia et al. show that reactive microglia switch states through reprogramming of histone modifications at st…
Population-level genomic analysis of immunoglobulin loci variation in rhesus macaques reveals extensive germline diversity
Contemporary immunology research commonly utilizes detailed analyses of immunoglobulin sequences; however, IG immunogenetics remain understudied in rhesus macaques (RMs). Peres et al. combine IG genomic and repertoire sequencing of >100 RMs to provide …
Immune signature-based uncoupling of checkpoint inhibitor efficacy and toxicity
Lucas et al. evaluate the interferon-gamma (IFN-γ) signature against toxicity and efficacy in four neoadjuvant melanoma immunotherapy regimens. IFN-γ-high scores associated with overall favorable efficacy but increased toxicity when anti-CTLA-4 was add…
From host to population: Bridging the viral immuno-evolutionary gap
Mandl and colleagues describe an important gap in our understanding of how antiviral immune mechanisms in individual hosts alter the evolutionary trajectories of viruses as they spread through populations. They propose that bold new experimental system…
Remodeling of skull bone channels regulates immune infiltration into the meninges during neuroinflammation
Skull marrow communicates with the meninges through bone channels, yet their formation and regulation remain poorly understood. Eme-Scolan et al. show that these channels undergo active remodeling during the neonatal period and can be reshaped by modul…
Transcription factor Maf promotes expression of repressor Zeb2 to drive microglia development in primitive hematopoiesis
How distinct hematopoietic waves generate specialized macrophage lineages remains unclear. Chen et al. identify separate transcriptional pathways controlling macrophage development during primitive versus definitive hematopoiesis and identify Maf and J…
Positioning and reversible suppression of CCR7+ dendritic cells in perivascular tumor niches shape cancer immunity
CCR7+ dendritic cells (DCs) are pivotal for antitumor immunity. Zitti, Duval et al. find that intratumoral CCR7+ DCs form perivascular hubs dependent on CCL19-CCR7 signaling. Regulatory T cells (Tregs) restrain immune function within these hubs, and bo…
Opposing functions of distinct regulatory T cell subsets in colorectal cancer
Huang et al. study the heterogeneity of regulatory T (Treg) cells in a genetic model of colorectal cancer (CRC) and find that interleukin (IL)-10− Treg cells promote tumor progression, whereas IL-10+ Treg cells restrain tumor growth by suppressing IL-1…
Innate type 2 lymphocytes trigger an inflammatory switch in alveolar macrophages
Monocyte-derived macrophages are highly plastic, whereas tissue-resident macrophages resist inflammatory reprogramming. Verwaerde et al. show that tissue-resident alveolar macrophages can be reprogrammed during type 2 pulmonary immune responses by acti…