Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3
By Cindy S. Ma, G. Chew, N. Simpson, Archana Priyadarshi, M. Wong, B. Grimbacher, D. Fulcher, S. Tangye, M. Cook. Journal of Experimental Medicine, 2008
710 citations recorded by the source corpus.
Hyper–immunoglobulin E syndrome (HIES) is a primary immune deficiency characterized by abnormal and devastating susceptibility to a narrow spectrum of infections, most commonly Staphylococcus aureus and Candida albicans. Recent investigations have identified mutations in STAT3 in the majority of HIES patients studied. Despite the identification of the genetic cause of HIES, the mechanisms underlying the pathological features of this disease remain to be elucidated. Here, we demonstrate a failure of CD4+ T cells harboring heterozygous STAT3 mutations to generate interleukin 17–secreting (i.e., T helper [Th]17) cells in vivo and in vitro due to a failure to express sufficient levels of the Th17-specific transcriptional regulator retinoid-related orphan receptor γt. Because Th17 cells are enriched for cells with specificities against fungal antigens, our results may explain the pattern of infection susceptibility characteristic of patients with HIES. Furthermore, they underscore the importance of Th17 responses in normal host defense against the common pathogens S. aureus and C. albicans.
Subfields: Immunology
View Paper: https://www.semanticscholar.org/paper/dc95995ca02f7c5d3d12a886eb2e2408e7d8cbe1
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Citations in the corpus
- Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis (2011, background): “These patients have very low proportions of circulating IL-17A– and IL-22– producing T cells, probably because of impaired responses to IL-6, IL-21, and/or IL-23 (de Beaucoudrey et al., 2008; Ma et al., 2008; Milner et al., 2008; Renner et al., 2008; Minegishi et al., 2009).”
- Diverse Targets of the Transcription Factor STAT3 Contribute to T Cell Pathogenicity and Homeostasis (2010, background): “Patients with Job’s or Hyper IgE Syndrome (HIES) have dominant-negative mutations of STAT3 and are deficient in Th17 cells, underscoring the close link between STAT3 and Th17 cells (Holland et al., 2007; Ma et al., 2008; Milner et al., 2008; Minegishi et al., 2007).”
- From Vaccines to Memory and Back (2010, neutral): “The protective nature of these polarized responses is underlined by studies of human immunodeficiencies, where patients with defective Th1 or Th17 responses suffer from mycobacterial or fungal infections, respectively (Ma et al., 2008; Milner et al., 2008).”
- Circulating Th17, Th22, and Th1 Cells Are Increased in Psoriasis (2009, neutral): “Furthermore, individuals with genetic mutations in STAT3 develop Job’s syndrome, also known as hyper-IgE syndrome, and are incapable of making Th17 cells (Ma et al., 2008; Milner et al., 2008).”
- Border patrol: regulation of immunity, inflammation and tissue homeostasis at barrier surfaces by IL-22 (2011, background): “These patients have impaired T H 17 differentiation and lower IL-22 productio”
- HIV and Tuberculosis: a Deadly Human Syndemic (2011, background): “Th17 cells recognize bacterial and fungal (and, less commonly, viral) antigens, secrete IL-17 and IL-22, and contribute to immunity to yeasts, extracellular bacteria (114, 166, 190), and, possibly, M.”
- Critical regulation of early Th17 cell differentiation by IL-1 signaling (2009, background): “We found that Th17 cells expressed higher amounts of IL-1R1 mRNA, which was dependent on STAT3, RORa, and RORgt.”