People & Ideas
María Mittelbrunn leads the Immunometabolism and Inflammation Laboratory at the Severo Ochoa Molecular Biology Center. Her lab takes a multidisciplinary approach to explore immunometabolism as a therapeutic target in the treatment of chronic inflammation and aging.
In this Viewpoint, we hear from a cross section of women, across multiple research fields, discussing their science and the process of setting up a lab as an independent researcher. As well as being able to celebrate the positives of becoming an independent researcher, we would also like to use this platform to discuss the unique challenges they face as women scientists in their respective scientific environments.
Great progress has been made over the past half-century, but TB remains a formidable global health problem. The Perspective summarizes much that has been learned and identifies key areas for which new knowledge is critically needed.
Brief Definitive Reports
Recurrent infection transiently expands human tissue T cells while maintaining long-term homeostasis
The immune cell compartment in human genital skin expands and contracts following HSV-2 reactivation, and includes cells recruited from circulation and proliferating cells. Despite frequent antigen exposure, tissue T cell number and phenotype remain stable in the long-term, likely driven at least in part by cell-extrinsic and cell-intrinsic regulatory mechanisms.
Maes et al. reveal an unexpected role of TAOK3 in regulating ST2+ regulatory T cells in mouse adipose tissue. Absence of TAOK3 sustains Tregs in obesity and improves metabolic dysfunction.
Globoid cell leukodystrophy (GLD) is an incurable genetic disease characterized by profound white matter loss and inflammation. This report identifies CD8+ T cells as a novel pathogenic process in the clinical development and neuropathology of this disease.
Human RELA dominant-negative mutations underlie type I interferonopathy with autoinflammation and autoimmunity
This report establishes a novel form of IEI due to DN RELA mutations as a cause of chronic mucocutaneous ulcerations with autoinflammatory and/or autoimmune manifestations. This also expands the clinical spectrum of human RELA-associated diseases.
Gervais et al. show that auto-Abs neutralizing type I IFNs and pre-existing infection underlie ∼40% of cases of West Nile virus (WNV) encephalitis. Blood and cerebrospinal fluid auto-Abs neutralize the protective activity of type I IFNs against WNV in vitro.
Loss-of-function mutations in the gene encoding the lysosomal nucleoside transporter SLC29A3 cause histiocytic diseases, collectively termed SLC29A3 disorders. Shibata et al. show that histiocytosis is driven by mouse TLR7 and human TLR8, endosomal sensors for nucleosides and oligoribonucleotides, in mice and humans, respectively.
Innate mononuclear phagocytic cells (MPS) in the nasal mucosa are the first to encounter inhaled allergens. MPS from allergic rhinitis patients showed a pro-inflammatory response during experimental allergen challenge, while clinically silent non-allergic controls displayed a tolerizing/anti-inflammatory response.
Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis
Neutrophil extracellular traps and extracellular histones potentiate Th17 inflammation and bone destruction in animal models of periodontitis. Findings in patients with periodontitis provide human relevance and support further exploration of NET-mediated pathology in human disease.
Wang et al. examined antibody and memory B cell responses to SARS-CoV-2 mRNA booster vaccination in the elderly. Their analysis revealed a small but significant decrease in memory B cell numbers with an altered antibody repertoire that may contribute to a higher risk for severe disease in the elderly.
Protein arginine methyltransferase 1 regulates B cell fate after positive selection in the germinal center in mice
Protein arginine methyltransferase 1 (PRMT1) is upregulated via Myc and mTORC1 during positive selection and influences germinal center B cell fate. PRMT1 promotes antibody affinity maturation by favoring dark zone fate and proliferation while limiting differentiation, two functions that are co-opted by mature B cell lymphoma cells.
Promiscuous recognition of MR1 by canonical MAIT TCRs endowed with dual reactivity to both microbial and self-antigens enables MAIT cell responses in the absence of microbial infection.
Cancer cell plasticity and MHC-II–mediated immune tolerance promote breast cancer metastasis to lymph nodes
Lei et al. uncover that a subpopulation of breast cancer cells in the lymph node is marked by MHC-II expression in the absence of costimulatory molecules, which causes the expansion of immunosuppressive regulatory T cells.
Xu et al. define Baf60c in skeletal myofibers as a critical regulator of muscle regeneration through Dkk3-mediated paracrine signaling on muscle stem cells. They also uncover that Baf60c interacts with transcription factor Six4 to synergistically suppress Dkk3 expression in myocytes.
Steady-state and emergency myelopoiesis require different rates of mature cell production to maintain or restore homeostasis. This study demonstrates that mitochondrial pyruvate is specifically required for steady-state but not emergency myelopoiesis. Reciprocally, glutaminolysis specifically promotes emergency but not steady-state myelopoiesis.
Correction: Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge