APRIL expression is upregulated in atopic dermatitis skin lesions and at sites of antigen driven allergic skin inflammation in mice.

Atopic dermatitis (AD) is the most common inflammatory skin disease. It is characterized by a defective skin barrier and a Th2 dominated skin inflammation. The TNF family member a proliferation-inducing ligand (APRIL) and its receptors transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI) and B cell maturation antigen (BCMA) are expressed by immune cells and epithelial cells including keratinocytes.

Deficiency of base excision repair enzyme NEIL3 drives increased predisposition to autoimmunity.

Alterations in the apoptosis of immune cells have been associated with autoimmunity. Here, we have identified a homozygous missense mutation in the gene encoding the base excision repair enzyme Nei endonuclease VIII-like 3 (NEIL3) that abolished enzymatic activity in 3 siblings from a consanguineous family. The NEIL3 mutation was associated with fatal recurrent infections, severe autoimmunity, hypogammaglobulinemia, and impaired B cell function in these individuals.

Heterozygosity for transmembrane activator and calcium modulator ligand interactor A144E causes haploinsufficiency and pneumococcal susceptibility in mice.

Background: The B-cell receptor transmembrane activator and calcium modulator ligand interactor (TACI) is important for T-independent antibody responses. One in 200 blood donors are heterozygous for the TACI A181E mutation.

Objective: We sought to investigate the effect on B-cell function of TACI A181E heterozygosity in reportedly healthy subjects and of the corresponding TACI A144E mutation in mice.

A missense mutation in TFRC, encoding transferrin receptor 1, causes combined immunodeficiency.

Patients with a combined immunodeficiency characterized by normal numbers but impaired function of T and B cells had a homozygous p.Tyr20His substitution in transferrin receptor 1 (TfR1), encoded by TFRC. The substitution disrupts the TfR1 internalization motif, resulting in defective receptor endocytosis and markedly increased TfR1 expression on the cell surface.