Research articles

How fibrosis and inflammation are integrated is not entirely clear. Here the authors show that profibrotic proximal tubular cells in the kidneys recruit basophils and activate them to produce interleukin-6 and drive T_H17 cell responses.

Around the world, governments are urging populations to receive a third COVID-19 vaccine dose. Here, the authors compare immunogenicity, reactogenicity and effectiveness of a third dose versus the second dose of the BNT162b2 vaccine in a large group of healthcare workers in Israel.

How ILC1s respond to cancer cells is somewhat controversial. Here, the authors show that IFNγ released by ILC1s can control acute myeloid leukemia by promoting leukemia stem cell apoptosis and favoring their differentiation into non-leukemic cells.

To determine how T cell lineage fates are determined in the thymus, Singer and colleagues generated ‘FlipFlop’ mice with a functionally reversed T cell immune system that distinguishes TCR signal strength versus TCR signal duration.

Blander and colleagues show that concurrent detection of LPS and bacterial RNA triggers the interaction of procaspase-11 with NLRP3, upstream of the activation of either receptor and before NLRP3–ASC oligomerization.

Cassatella and colleagues identify CD66b⁻CD64^dimCD115⁻ cells in the human bone marrow as the earliest neutrophil-committed progenitor cells described to date.

How the mitochondrial electron transport chain (ETC) interacts with the NLRP3 inflammasome is somewhat unclear. Here the authors use individual complex inhibitors and new genetic models to show that ETC is critical in providing ATP via the phosphocreatine shuttle to activate the NLRP3 inflammasome.

Malek and colleagues describe the longitudinal transcriptional and epigenetic changes occurring in regulatory T cells following in vivo stimulation with IL-2 or the biologic IL-2–CD25.

Perry et al. demonstrate that regulatory T (T_reg) cell function is restrained by the cell-autonomous action of the checkpoint inhibitor molecule PD-1. This PD-1-dependent mechanism tunes T_reg cell function during homeostasis and infection.

Vignali and colleagues show that the inhibitory receptor LAG3 interferes with TCR signaling and T cell activation by lowering the pH at the immune synapse, which causes the dissociation of the tyrosine kinase Lck from the CD4 or CD8 co-receptor.

Schumacher and colleagues have designed a reporter system that allows in vivo tracking of replicative history over many cell generations. Using this system to study acute T cell responses, they uncover substantial diversity in past division of central memory CD8⁺ T cells and its link to cell state and recall potential.

Thomas and colleagues describe how multiple SARS-CoV-2 antigen exposures, including mRNA vaccine boosters, primary infection and breakthrough infection, shape T cell immunity.

Tussiwand and colleagues show that an uncommitted precursor expressing the lymphoid-specific factor TdT generates a large fraction of myeloid and a substantial fraction of erythro-megakaryocyte cells.

Nie et al. show that the transcription factor LRF, by upregulating expression of the integrin gene Itgb7, imprints thymic precursors of CD8αα⁺ intraepithelial lymphocytes for eventual seeding of the gut tissues.

Rinkevich and colleagues show that preexisting matrix is transferred by neutrophils across organs into injured sites in a manner dependent on integrin activation.

Fabry and colleagues show that cribriform plate-resident lymphatic endothelial cells respond to neuroinflammatory signals by inducing functional changes that enhance antigen capture and presentation from the cerebrospinal fluid and promote leukocyte interactions within the central nervous system.

Nahrendorf and colleagues show that B cells in the bone marrow are an important source of the neurotransmitter acetylcholine, which limits hematopoiesis through modulating the signals produced by the bone marrow stromal niche during steady-state and emergency hematopoiesis.

RNA vaccines have been associated with high reactogenicity. Mellman and colleagues demonstrate that lipid-formulated RNA vaccines trigger IL-1 production and inflammation in humans but this pathway is dampened in mice.

Colonna and colleagues present a genome-wide characterization of DNA methylation and hydroxymethylation in innate lymphocytes and identify differentially methylated and hydroxymethylated regions between NK cells, ILC2s and ILC3s.

Tumor-associated macrophages can restrict antitumor responses. Barreira da Silva and colleagues demonstrate that the intracellular enzyme QPCTL supports recruitment of immunomodulatory macrophages to the tumor microenvironment and its targeting can enhance tumor control.