Detection of pathogens, such as bacteria and viruses, by pattern recognition receptors (PRRs) triggers activation of components of immune cell defense pathways such as the inflammasome, type I interferon, and STING. This culminates in proinflammatory cell death, termed pyroptosis, and release of the coagulation activator, tissue factor (TF). This process of immune cell activation triggering coagulation, termed immunothrombosis, is a hallmark of coagulopathies such as sepsis and disseminated intravascular coagulation.

The pancreas plays a pivotal role in protecting the gastrointestinal tract from the breakdown of the mucosal barrier and the expansion of pathobionts that can lead to systemic disease. This crosstalk highlights the emerging concept of a pancreas-gut axis in the control of host responses to infection.

The differentiation and function of dermal CD11b^low cDC2s requires the cytokine IL-13 and the transcription factors STAT6 and KLF4. Here, we discuss the properties of this skin-unique cDC2 population in the context of cDC2 heterogeneity across different tissues, the development of Th2 immune responses, and inflammatory skin disease.

The RNA-binding protein PTBP1 is essential during early events following T-cell activation by regulating the alternative splicing of genes including that encoding calcineurin Aβ isoforms. These findings provide insight into how PTBP1 regulates gene expression essential for the optimal activation of T cells.

Human type 1 conventional dendritic cells (cDC1s) display constitutive activation of the IRE1/XBP1s axis of the UPR in steady state. Proinflammatory cytokine production by activated cDC1s is partly dampened upon inhibition of the IRE1 RNase domain, uncovering a role of the pathway in the biology of the human DC lineage.

Earlier studies showed that antigen receptor signal strength can dictate Th1/Th2 polarization. Prolonged antigen receptor signaling induces the expression of a transcription factor, SHN-3, which is required for initial Th2-cell differentiation.  Loss of SHN-3 expression causes a reduction in IL-4 production and causes Th1-dominant in vivo immune responses.

Tissue-resident memory T cells (Trm) permanently lodge themselves in peripheral tissues to capture invading pathogens. We found that the transcription factors Hobit and Blimp-1 already acted in Trm precursors to suppress tissue-exit pathways. Our findings imply that establishment of the Trm lineage requires lodgment of their precursors early after infection.

Host blood-derived biomarkers based on tuberculosis parsimonious transcriptomic signatures showed potential to predict and diagnose immune reconstitution inflammatory syndrome upon initiation of antiretroviral therapy in children and adults with HIV.

Autoantibodies capable of neutralizing multiple IFN-α subtypes and IFN-ω can be found in severe COVID-19 patients, preferentially males. Anti-IFN-I neutralizing antibodies (NAB) positive patients present a defective IFN response and have raised levels of biochemical and hematological parameters predictive of severe COVID-19.

MSC-sEV regulated the differentiation and function of dendritic cells in allergic rhinitis.  Peripheral monocytes treated with GM-CSF, IL-4, and LPS differentiated into dendritic cells. DCs treated with MSC-sEV inhibited the type 2 immune response from allergic rhinits. sEV-mDC exhibited a regulatory phenotype by the production of IL-10 and induced Treg cells. GM-CSF: granulocyte-macrophage colony-stimulating factor, LPS: lipopolysaccharide, mDCs: mature dendritic cells, MSC: mesenchymal stromal cells, sEV: small extracellular vesicles, Treg: regulatory T.

A. In human monocytes, IL-37 cleavage occurs constitutively but not at positions D20 or V46. B. Long-term LPS stimulation induces mature IL-37 release independently of alternative NLRP3 inflammasome but dependent on membrane permeability. C. Mature IL-37 release is mediated by canonical NLRP3 inflammasome activation, gasdermin-D, and membrane permeability.

Low level of CD5 expression identified phenotypically dormant T cells with autoimmune potential, which was revealed upon cell transfer. Transcriptional signature indicated stem-cell memory-like phenotype and was similar to low-affinity insulin-specific T cells, suggesting that TCR affinity guides autoimmune T-cell fate decisions and stem-like capacity.

Patients with common variable immunodeficiency with no previous genetic diagnosis presenting additionally one autoimmune symptom were compared to healthy subjects. Circulating follicular helper T (Tfh) cells were analyzed for their phenotype and function by flow cytometry, while their transcriptome was determined with RNA seq. Genetic analysis was performed by WES and validated by Sanger Sequencing. An integrated pipeline led to the identification of a cluster of patients characterized by a Th1 Tfh signature, elevated plasma CXCL13 levels, shortened telomeres, and enlarged lymph nodes and spleen. Rare monoallelic mutations in RTEL1 were identified as a possible common denominator. Further analyses revealed Tfh replicative exhaustion as a possible underlying mechanism.