Activation of the cGAS/STING Axis in Genome-Damaged Hematopoietic Cells Does Not Impact Blood Cell Formation or Leukemogenesis.

Unlabelled: Genome damage is a main driver of malignant transformation, but it also induces aberrant inflammation via the cGAS/STING DNA-sensing pathway. Activation of cGAS/STING can trigger cell death and senescence, thereby potentially eliminating genome-damaged cells and preventing against malignant transformation. Here, we report that defective ribonucleotide excision repair (RER) in the hematopoietic system caused genome instability with concomitant activation of the cGAS/STING axis and compromised hematopoietic stem cell function, ultimately resulting in leukemogenesis.

Novel mutation and expanding phenotype in IRF2BP2 deficiency.

Objectives: Inborn errors of immunity manifest with susceptibility to infection but may also present with immune dysregulation only. According to the European Society for Immunodeficiencies Registry about 50% of inborn errors of immunity are classified as common variable immunodeficiencies (CVID). In only few CVID patients are monogenic causes identified.

Unimpaired Responses to Vaccination With Protein Antigen Plus Adjuvant in Mice With Kit-Independent Mast Cell Deficiency.

Innate inflammatory responses are crucial for induction and regulation of T cell and antibody responses. Mast cell (MC)-deficient mutant mice showed impaired adaptive immunity, suggesting that MCs provide essential adjuvant activities, and pharmacological MC activation was proposed as a new adjuvant principle. However, the mutations result in complex alterations of the immune system in addition to MC deficiency.

Human 6-sulfo LacNAc-expressing dendritic cells are principal producers of early interleukin-12 and are controlled by erythrocytes.

Early and high-level production of IL-12 is crucial for effective immune responses against pathogens. Up until now, the cells providing this initial IL-12 have remained elusive. Here we show that a subset of human blood dendritic cells (DC) is the principal and primary source of IL-12p70 when blood leukocytes are stimulated with the TLR4-ligand LPS or with CD40-ligand.