Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Allergy, Immunology, Leaky severe combined immunodeficiency, Artemis, regulatory T cell, cytotoxic T-lymphocyte-associated protein 4, immune dysregulation, OMENN-SYNDROME, V(D)J RECOMBINATION, ARTEMIS, CELLS, MUTATIONS, FOXP3(+), HOMEOSTASIS, DEFICIENCY, PHENOTYPE, APOPTOSIS, Abatacept, Animals, B-Lymphocytes, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Endonucleases, Humans, Inflammation, Lymphocyte Activation, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nuclear Proteins, Recombinational DNA Repair, Severe Combined Immunodeficiency, T-Lymphocytes, 1107 Immunology, 3204 Immunology

Abstract:

Severe combined immunodeficiency (SCID) can be caused by loss-of-function mutations in genes involved in the DNA recombination machinery, such as RAG1, RAG2 or DCLRE1C. Defective DNA recombination causes a developmental block in T cells and B cells, resulting in high susceptibility to infections. Hypomorphic mutations in the same genes can also give a partial loss of T cells, in a spectrum including leaky SCID (LS) and Omenn syndrome (OS). These patients not only develop life-threatening infections due to immunodeficiency, but also develop inflammatory/autoimmune conditions due to the presence of autoreactive T cells.