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TNIP1, a previously identified risk factor for autoimmunity, regulates mitochondrial autophagosomal trafficking. Missense mutations in TNIP1 disrupt this regulatory function, yielding a B cell-intrinsic predisposition for TLR7-mediated autoimmunity characterized by IgG4 autoantibodies and the expansion of age-associated B cells.
Why some individuals ‘resist’ infection with Mycobacterium tuberculosis (Mtb) has been an enigma. Enriched T cell phenotypes have now been linked to ‘resistance’ to Mtb infection and disease across multiple cohorts.
The G protein Gα13 is frequently lost in germinal center (GC) B cell-derived lymphomas. Mice that lack Gα13 exhibit increased proliferation of GC B cells in gut-draining lymph nodes where they go on to develop lymphomas. Dietary glutamine drives the proliferation of mucosal GC B cells that lack Gα13, potentially explaining the gut tropism of these lymphomas.
Immunological imprinting early in life has been proposed to influence the risk of infection by influenza viruses later on — but hard evidence for this has been lacking. A new study now shows how this can occur for influenza B viruses.
We constructed a humanized (THX) mouse by grafting non-γ-irradiated, genetically myeloablated immunodeficient mouse neonates with human cord blood CD34+ cells, followed by 17β-estradiol hormonal conditioning. THX mice develop a human lymphoid and myeloid immune system, mount mature antibacterial and antiviral neutralizing antibody responses, and are amenable to develop lupus autoimmunity.
We performed transcriptional and chromatin accessibility profiling of TH17 cells to distinguish the pathways that regulate pathogenic versus non-pathogenic TH17 cell subsets. We show that TH17 cell functional heterogeneity is linked to distinct regulatory programs that are shared between TH17 cells and other CD4+ T cell states. BACH2 was identified as a key regulator of TH17 cell-mediated autoimmunity.
The EMBO workshop ‘Pathogen Immunity and Signaling’, held in San Servolo, Italy, from 8 to 12 April 2024, aimed to discuss cutting-edge advances in the understanding of antimicrobial defense mechanisms.
Our study shows that each stimulation experienced by memory B cells is epigenetically recorded in an IRF4-dependent manner, which determines the relative levels of BLIMP1 and BACH2 in B cells, and in turn dictates the likelihood that a memory B cell enters a germinal center or becomes a plasma cell after re-stimulation.
Extrafollicular and germinal center reactions are considered to represent sequential phases of a primary B cell response. A study now demonstrates the ability of autocrine IL-12 to promote extrafollicular differentiation into plasmablasts, while inhibiting germinal center responses.
Innate lymphoid cells (ILCs) exhibit remarkable plasticity, which makes using definitive markers to distinguish non-cytotoxic ILC1s and NK cells across different tissues difficult. New research now shows how the tissue microenvironments imprint diverse phenotypes that result in ILC1s and NK cells imitating each other.
The molecular basis for the efficacy of ZED1227 — a transglutaminase 2 inhibitor — in celiac disease is unknown. We show that orally administered ZED1227 effectively prevented gluten-induced intestinal damage and inflammation at the transcriptome level, and that individuals with high-risk HLA class II celiac disease consistently display a more ‘deteriorated’ molecular phenotype.
IL-1R1 signaling in neural stem cells reduces hippocampal neurogenesis in adult mice, potentially affecting learning and memory. Using a new mouse model, we report that IL-1β drives cognitive impairment after infection with SARS-CoV-2, and that IL-1β-driven cognitive impairment can be prevented by vaccination, even in cases of breakthrough infection.
Improved understanding of CD8+ T cell function during HIV infection is vital to designing an HIV cure. We have identified a subset of lymph node CD8+ T cells that demonstrate simultaneous stem-like and effector properties and are strongly associated with viral control during SIV and HIV infection.
In this Review, the authors summarize the literature around immune cancer cell STING signaling and how it is finely balanced between pro-tumorigenic and anti-tumorigenic functions.
Dendritic cells migrate to and from lymph nodes in response to chemokine gradients.Data now show that steady-state migration of these cells can be triggered by a mechanosensitive pathway.
Variation in inter-individual immune phenotypes can be influenced by both genetics and environmental factors. Using a range of different inbred strains of mice that were kept either indoors or in an outdoor enclosure — ‘rewilded’ — we found that both genetics and environment combine to dictate an individual’s immune profile and outcome to parasitic helminth infections.
Adaptation to hypoxia and immune escape are two hallmarks of Mycobacterium tuberculosis infection. The d-serine isomer has now been identified as a factor produced by M. tuberculosis upon hypoxic conditions, dampening CD8+ T cell responses.
The developmental relationship between natural killer (NK) cells and other innate lymphoid cells (ILCs) has been a subject of scrutiny in recent years. Two studies now identify an early precursor committed to the NK cell lineage.
