Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
APLAID is a very rare autoinflammatory disease thought to be caused by mutations in PLCG2. A mouse model of APLAID recapitulates clinical features of the disease, and identifies a crucial function for G-CSF that might be targeted therapeutically.
The immune system is not immune to sex differences. New research now uncovers the molecular mechanisms that underlie sex-based differences during antiviral immune responses.
Mononuclear phagocyte proliferation is thought to be limited to myeloid progenitor cells and mature macrophages. However, availability within an interstitial macrophage niche permits the proliferation of monocytes in the lung before macrophage differentiation.
When an interstitial macrophage niche is empty, classical monocytes can proliferate locally in a manner that is restricted by the transcription factor MAFB, before undergoing differentiation into distinct macrophage subsets. These findings reveal a new function of monocytes and highlight the complex regulation of proliferation and differentiation during macrophage development.
APLAID is a rare autoinflammatory disorder driven by mutations in PLCG2. Here the authors provide a new mouse model using the human APLAID p.Ser707Tyr mutation. The mouse recapitulates clinical features of APLAID that can be prevented by anti-G-CSF. Individuals with APLAID were also shown to have high circulating levels of G-CSF suggesting this might be a suitable target for the clinic.
Capturing cell organization in the tumor microenvironment using spatial proteomics can provide insight into the disease. A pair of studies applying this to advanced lung and brain tumors identifies organizational immune hallmarks that are associated with patient outcomes.
Antibody dynamics resulting from sequential immunization are complex, limiting the study of concepts such as ‘original antigenic sin’. Here, molecular fate-mapping defines an ‘addiction’ of boosted antibodies to primary clones, and OAS-like suppression of new clones, to a degree inversely related to boosting antigenic distance.
Taking advantage of intersectional genetics, Valente et al. report a novel strategy for tracking plasmacytoid dendritic cells (DCs) that enables their discrimination from conventional DCs and plasmacytoid DC–like cells, as well as transitional DCs.
NK cells require an immunological synapse to kill cancer cells and these synapses have been shown to have membranous protrusions. Here the authors use cutting-edge imaging and other techniques to show that tumor serine metabolism results in a reduction in NK cell sphingomyelin content and a lack of these membranous protrusions, which could contribute to a failure to kill cancer cells.
Singer and colleagues show that the developmental fate of autoreactive CD4+ thymocytes is determined by the timing and duration of agonist signaling. Early agonist signaling induces clonal deletion, whereas late agonist signaling induces differentiation into Foxp3+ Treg cells or IL-2+ Teff cells depending on whether TGF-β disrupts TCR signaling.
Hidalgo and colleagues discuss general functional features of the neutrophil compartment that may be relevant in physiological scenarios such as specialization in naïve tissues, diversification and functional bias in inflammatory sites.
The NLRP10 protein is found to form an inflammasome complex in response to mitochondrial damage. Loss of NLRP10 from colonic epithelia promotes inflammatory bowel disease in a mouse model, while a variant predisposing to atopic dermatitis also shows loss of function.
The authors show that Nlrp10 can form a functional inflammasome in vitro and ex vivo, and that this inflammasome is protective in dextran sodium sulfate-induced colitis in mice.
NLRP10 has been considered as an inflammasome inhibitor. Here the authors show that upon mitochondrial rupture, NLRP10 assembles a canonical inflammasome and is highly expressed in differentiated keratinocytes, possibly supporting skin homeostasis.
Kamiya and colleagues examine the effects of chronic social-defeat stress on the intestinal microbiome and show a pathological role played by dectin-1 and interleukin-17 expressed by gut γδ T cells on this behavioral vulnerability.
