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Genetic lineage tracing and progenitor and multilineage fate mapping after single hematopoietic stem cell (HSC) transplantations identify two distinct HSC-progenitor trajectories for the replenishment of platelets in mice. These pathways include a slower multilineage pathway and a faster platelet-restricted or biased pathway, initiated by distinct and non-hierarchically related HSCs.
This work identifies two rare genetic variants of UNC93B1 that contribute to the development of childhood-onset lupus. Mice that expressed one of these variants developed a lupus-like disease. UNC93B1 is known to regulate the localization of Toll-like receptors (TLRs) to the endosome, and UNC93B1 variants resulted in enhanced responses to TLR7 and TLR8 agonists.
Structure-guided protein design enables germline-targeting immunization strategies to generate broadly neutralizing antibodies against MPER, a region of the HIV envelope glycoprotein that is functionally important and highly conserved, but a challenging target for antibody responses.
Immune cells coordinate β-cell insulin secretion to regulate glucose levels and promote type I interferon production to control systemic viral infection.
CAR T cell technology is being extended beyond the treatment of cancer. New data show that it might also treat allergic asthma, with a single infusion sufficient to prevent pathology for over a year in mice.
The National Institute of Allergy and Infectious Diseases (NIAID) hosted a two-day virtual workshop on leveraging microbial exposure to improve mouse models of human immune status and disease. The workshop’s objective was to evaluate the current state of knowledge in the field and to identify gaps, challenges and future directions.
How aging, immunity and cancer are related is incompletely understood. Data now show altered differentiation and loss of function of tumor-infiltrating T cells with aging. So-called TTAD cells seem to be involved.
Our work identifies previously unrecognized functional heterogeneity in tissue-resident interstitial macrophages. We have identified ten macrophage subsets, each thought to specifically contribute to recruiting and organizing cell types within tissues. Moreover, our findings suggest the diversity and division of labor extend to other macrophage populations previously considered homogeneous.
In this Review, the authors analyze evidence for autoimmunity against components of antimicrobial immunity, metaphorically represented by the mythical ouroboros snake eating its own tail.
Homeostatic immune cells remain perpetually vigilant against pathogens. We found that baseline JAK–STAT signaling supports the characteristic transcriptional and epigenetic state of homeostatic T cells and macrophages in mice. JAK–STAT signaling under homeostatic conditions was driven by signals from healthy tissue and did not require external immune stimuli.
We report two patients with biallelic SHARPIN deficiency, which manifests with autoinflammation and B cell immunodeficiency and is phenotypically distinct from Sharpin deficiency in mice. In one patient, there was a significant shift from pro-survival signaling to cell-death signaling in fibroblasts and lymphoblasts induced by members of the TNF cytokine superfamily, accounting for the autoinflammation and immunodeficiency. Targeted therapy with TNF inhibitors had a dramatic beneficial effect.
The transient expression of CD61 and its unconventional pairing with CD103 at the immune synapse enhances T cell receptor signaling, improves anti-tumor cytotoxicity and mitigates tumor growth. Clinically, CD61+ tumor infiltrating lymphocytes (TILs) exhibit enhanced effector functions and show limited cellular exhaustion.
The microbiome is known to affect antitumor immune responses, but how this occurs is unclear. Rhamnose-rich polysaccharides (RHP) from a commensal strain of Lactiplantibacillus plantarum have now been shown to induce iron sequestration by tumor macrophages, thereby limiting tumor growth and promoting antitumor immunity.
The intestinal immune response is tightly controlled to limit inflammation, largely by the cytokine IL-10, which prevents colitis. We report that the transcription factors c-MAF and BLIMP-1 induced IL-10 in T cells in the colon, but also acted to negatively regulate distinct cytokine pathways to restrict pathobiont-induced colitis.
Age is the single greatest risk factor driving mortality after encounter with SARS-CoV-2. A new study shows that the composition of nasal epithelial cells varies across ages, facilitating SARS-CoV-2 growth and spread in older people.
Specialized T cell effector functions depend upon pre-established chromatin state. Cooperativity among PU.1, RUNX1 and BCL11B directs SWI–SNF complex recruitment to carry out chromatin priming at T cell effector loci during early thymic development.
MEF2C is a transcription factor that has known functions in a variety of cell types, but it has not yet been ascribed a role in natural killer cells. Data now show that MEF2C promotes the functional responses of human and murine natural killer cells by controlling their metabolic programs.
In this study, we use a transcriptomic approach as a starting point to explore the heterogeneity of human GATA3-expressing lymphocytes across different tissues and disease contexts. We identify, characterize and functionally validate an abundant progenitor-like memory T cell population with the potential to sustain pathogenic TH2 cell inflammation.