Defects along the TH17 differentiation pathway underlie genetically distinct forms of the hyper IgE syndrome

Khatib, Shadi Al; Keleş, Sevgi; Garcia-Lloret, Maria; Karakoç-Aydıner, Elif; Reisli, İsmail; Artaç, Hasibe; Camcioğlu, Yıldız; Çokuğraş, Haluk; Somer, Ayper; Kütükçüler, Necil; Yılmaz, Mustafa; İkincioğulları, Aydan; Yegin, Olcay; Yüksek, Mutlu; Genel, Ferah; Kucukosmanoglu, Ercan; Baki, Ali; Bahceciler, Nerin N.; Rambhatla, Anupama; Nickerson, Derek W.; McGhee, Sean; Barlan, Işıl; Chatila, Talal A.

doi:10.1016/j.jaci.2009.05.004

Cited by 92 publications

(84 citation statements)

References 32 publications

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“…Defects in T lymphocyte IL-17 production also occurs in DOCK8 deficiency (Fig. 2), but unlike STAT3 mutations, which impair the initial steps in Th17 differentiation, DOCK8-deficient patients have defects in Th17 cell terminal differentiation and persistence (Khatib et al 2009). DOCK8 deficiency is caused by homozygous or compound heterozygous point mutations as well as large deletions in DOCK8 with resultant reduced or absent protein (Engelhardt et al 2009;Zhang et al 2009).…”

Section: Dock8 and Tyk2 Deficiencies (Autosomal Recessive Hies)mentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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Correspondence: lionakism@niaid.nih.gov A recent surge in newly described inborn errors of immune function-related genes that result in susceptibility to fungal disease has greatly enhanced our understanding of the cellular and molecular basis of antifungal immune responses. Characterization of single-gene defects that predispose to various combinations of superficial and deep-seated infections caused by yeasts, molds, and dimorphic fungi has unmasked the critical role of novel molecules and signaling pathways in mucosal and systemic antifungal host defense. These experiments of nature offer a unique opportunity for developing new knowledge in immunological research and form the foundation for devising immune-based therapeutic approaches for patients infected with fungal pathogens.

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Section: Dock8 and Tyk2 Deficiencies (Autosomal Recessive Hies)mentioning

confidence: 99%

Mendelian Genetics of Human Susceptibility to Fungal Infection

Lionakis

Netea

Holland

2014

Cold Spring Harbor Perspectives in Medicine

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“…Patients with DOCK8 deficiency do not have the same skeletal findings, such as fractures, scoliosis and retention of primary dentition, which subjects with STAT3 deficiency do [2,23,26]. There may be some developmental or cognitive delay, but this has not been formally ascertained.…”

Section: Dock8 In Non-human Model Systemsmentioning

confidence: 99%

DOCK8 Immune Deficiency as a Model for Primary Cytoskeletal Dysfunction

McGhee

Chatila

2010

Disease Markers

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Abstract. DOCK8 deficiency is a newly described primary immune deficiency resulting in profound susceptibility to cutaneous viral infections, elevated IgE levels, and eosinophilia, but lacking in the skeletal manifestations commonly seen in hyper IgE syndrome, which it otherwise resembles. Although little is known about the DOCK8 protein, it resembles other atypical guanine exchange factors in the DOCK family, and is known to bind to CDC42. This suggests that a likely role for DOCK8 is in modulating signals that trigger cytoskeletal reorganization. As a result, DOCK8 may also be related to other immune deficiencies that involve the cytoskeleton and Rho GTPase signaling pathways, such as Wiskott-Aldrich syndrome and Rac2 deficiency.

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“…Although identified as a primary immunodeficiency, HIES involves also non-immunologic abnormalities, primarily in dentition, connective tissues and bones [1][2][3][4][5][6][7]. In view of the phenotypic variability of the disease, a scor-HIES was provided by publications documenting a deficiency in T helper 17 (Th17) cells in HIES patients, and showing that HIES T cells are impaired in production of Th17 cytokines [12,13,[16][17][18]. In addition, it was suggested that the STAT3 mutations may lead to increased IgE levels and to down-regulation of inflammatory responses in HIES patients [10,11].…”

Section: Introductionmentioning

confidence: 99%