期刊
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
卷 21, 期 23, 页码 -出版社
MDPI
DOI: 10.3390/ijms21239152
关键词
hyper-immunoglobulin E syndrome (HIES); primary immunodeficiency disease; Staphylococcus aureus; signal transducer and activator of transcription 3; T helper 17 (T(H)17) cell; chemokines; antimicrobial peptides; staphylococcal lung and skin infections
资金
- NIH (National Institute of Health) [R01 AI127406]
Hyper-immunoglobulin E syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent Staphylococcus aureus (S. aureus) infections, eczema, skeletal abnormalities and high titers of serum immunoglobulin E. Although the genetic basis of HIES was not known for almost a half century, HIES most frequently exhibits autosomal dominant trait that is transmitted with variable expressivity. Careful genetic studies in recent years identified dominant-negative mutations in human signal transducer and activator of transcription 3 (STAT3) gene as the cause of sporadic and dominant forms of HIES. The STAT3 mutations were localized to DNA-binding, SRC homology 2 (SH2) and transactivating domains and disrupted T helper 17 (T(H)17) cell differentiation and downstream expression of T(H)17 cytokines IL-17 and IL-22. Deficiency of IL-17 and IL-22 in turn is responsible for suboptimal expression of anti-staphylococcal host factors, such as neutrophil-recruiting chemokines and antimicrobial peptides, by human keratinocytes and bronchial epithelial cells. T(H)17 cytokines deficiency thereby explains the recurrent staphylococcal lung and skin infections of HIES patients.
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