TCR Signaling Abnormalities in Human Th2-Associated Atopic Disease

• Published in: Frontiers in immunology Vol. 9; p. 719
• Main Author: Milner, Joshua D.
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 16.04.2018
• Subjects: Actins - metabolism; atopic disease; Biomarkers; Cells, Cultured; Coculture Techniques; Cytoskeleton - metabolism; Dendritic Cells - immunology; Dendritic Cells - metabolism; Humans; Hypersensitivity, Immediate - genetics; Hypersensitivity, Immediate - immunology; Hypersensitivity, Immediate - metabolism; Immunology; Leukocytes, Mononuclear - immunology; Leukocytes, Mononuclear - metabolism; Lymphocyte Activation - genetics; Lymphocyte Activation - immunology; monogenic syndromes; Mutation; Phenotype; primary immunodeficiencies; Receptors, Antigen, T-Cell - genetics; Receptors, Antigen, T-Cell - metabolism; Signal Transduction; signaling pathways; T-cell receptor repertoire; Th2 Cells - immunology; Th2 Cells - metabolism; T-cell receptor repertoire; monogenic syndromes; atopic disease; primary immunodeficiencies; signaling pathways
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2018.00719

Stimulation of naïve CD4 T cells with weak T cell receptor agonists even in the absence of T helper-skewing cytokines can result in IL-4 production which can drive a Th2 response. Evidence for the consequences of such a phenomenon can be found in a number of mouse models and, importantly, a series of monogenic human diseases associated with significant atopy which are caused by mutations in the T cell receptor signaling cascade. Such diseases can help understand how Th2 responses evolve in humans, and potentially provide insight into therapeutic interventions.