Volume 23 Issue 7, July 2022

In airway epithelial cells, exposure to allergen proteases induces the stress granules-mediated transfer of IL-33 from the nucleus to the cytoplasm and extracellular release through gasdermin D pores containing a newly described active fragment.

Inflamed tissue has a special milieu, with hypoxia, high levels of metabolites from anaerobic glycolysis, and acidosis. Stimulation of a proton-activated receptor, TDAG8 (GPR65), in T cells has an important role in inflammatory bowel disease by balancing pro- and anti-inflammatory signals.

Lymphocyte activation gene 3 (LAG3) is an important checkpoint inhibitor molecule of immunotherapeutic interest. New crystal structures of LAG3 provide important insight into its molecular architecture, laying the groundwork for future basic and applied investigations.

Regulatory T cells that express high levels of IL-1R and ICOS display transcriptional features of antigen specificity, are highly suppressive and distinguish tumors from non-malignant inflamed tissues

Extrathymic MHCII⁺Rorc⁺ Aire-expressing cells that share characteristics with type 3 innate lymphoid cells (ILC3s) internalize C. albicans and present its antigens, priming the development of Candida-specific T_H17 cells.

Using high-resolution molecular and optical mapping of the three-dimensional genome, we found that the transcription factor TCF-1 is linked to changes in the structure of topologically associating domains in T cell progenitors that lead to interactions between previously insulated regulatory elements and target genes at late stages of T cell development.

A single-cell sequencing study shows that the human memory B cell repertoire is dominated by large IgM, IgG2 and IgA immunoglobulin families, whereas IgG1 families, including those specific for recall antigens, are of a small size. Multi-year analysis shows that memory B cell families are highly stable and that plasmablasts of T cell–independent and T cell–dependent isotypes are produced in a recurrent manner.

Crystal structures of the immune checkpoint protein LAG3 reveal critical binding interfaces for inhibitory antibodies and cellular ligands, such as FGL1 and MHC class II molecules. These structures provide insight into the dimeric assembly of LAG3 proteins on the surface of T cells and suggest FGL1-induced clustering as an immunomodulatory mechanism.

Instructed by locally increased levels of glucocorticoids in the skin after acute hair loss, regulatory T cells communicate with hair follicle stem cells by producing TGFβ3 to stimulate stem-cell proliferation and hair regrowth.

Qi et al. provide an in-depth analysis of antibody responses generated in response to SARS-CoV-2.

Sun and colleagues describe that the secretion of interleukin-33 is dependent on a p40 N-terminal fragment of gasdermin D, whose generation is independent of inflammatory caspase-1 and caspase-11.

LAG3 inhibits T cell activation, but exactly how it does so has been unclear given a lack of structural information. Here the authors provide the crystal structure of the human and mouse LAG3 ectodomains, showing how they interact with known ligands and antibodies.

Breed et al. identify a subset of thymic SIRPα⁺ cDC2 dendritic cells that express CD301b, induced by type II cytokines, and high amounts of MHC-II. They find that the deletion of these cells can alter thymic CD4-single-positive repertoires, suggesting that they contribute to thymic tolerance.

Vahedi and colleagues show that TCF-1 promotes T cell development by minimizing the spatial distance between regulatory elements that are located within insulated neighborhoods in progenitor cells and are required for the expression of T cell genes.

Extracellular microenvironments are more acidic upon tissue damage or in tumors. Xavier and colleagues identify a role for the pH-sensitive, G protein-coupled receptor GPR65 in multiple aspects of immune cell lipid metabolism, disruption of which leads to chronic inflammatory responses.

Lanzavecchia and colleagues use single-cell B cell receptor sequencing to examine the clonal structure, stability and dynamics of the B cell repertoire and the relationship between memory B cells and newly generated plasma cells in humans.

Skin T_reg cell crosstalk with hair-follicle stem cells (HFSCs) can control hair regrowth. Here the authors show that glucocorticoid receptor signaling in skin T_reg cells induces TGF-β3, which in turn facilitates HFSC proliferation.

Abramson and colleagues show that Aire⁺MHCII⁺ ILC3s sense, internalize and present Candida albicans and modulate the induction of C. albicans-specific T_H17 cells.

Shi and colleagues describe a subset of erythroid precursors with immune characteristics that can be isolated from the yolk sac to the adult bone marrow stages during human ontogenesis.

Goldrath and colleagues define the diversity of gene expression and genome accessibility in mouse CD8⁺ T_RM cells in distinct tissues and identify molecules critical forgeneration of CD8⁺ T_RM cells in response to acute viral infection.