Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/27554822http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/27554822http://www.w3.org/2000/01/rdf-schema#comment"

Background

Dedicator of cytokinesis 8 (DOCK8) deficiency is a combined immunodeficiency caused by autosomal recessive loss-of-function mutations in DOCK8. This disorder is characterized by recurrent cutaneous infections, increased serum IgE levels, and severe atopic disease, including food-induced anaphylaxis. However, the contribution of defects in CD4+ T cells to disease pathogenesis in these patients has not been thoroughly investigated.

Objective

We sought to investigate the phenotype and function of DOCK8-deficient CD4+ T cells to determine (1) intrinsic and extrinsic CD4+ T-cell defects and (2) how defects account for the clinical features of DOCK8 deficiency.

Methods

We performed in-depth analysis of the CD4+ T-cell compartment of DOCK8-deficient patients. We enumerated subsets of CD4+ T helper cells and assessed cytokine production and transcription factor expression. Finally, we determined the levels of IgE specific for staple foods and house dust mite allergens in DOCK8-deficient patients and healthy control subjects.

Results

DOCK8-deficient memory CD4+ T cells were biased toward a TH2 type, and this was at the expense of TH1 and TH17 cells. In vitro polarization of DOCK8-deficient naive CD4+ T cells revealed the TH2 bias and TH17 defect to be T-cell intrinsic. Examination of allergen-specific IgE revealed plasma IgE from DOCK8-deficient patients is directed against staple food antigens but not house dust mites.

Conclusion

Investigations into the DOCK8-deficient CD4+ T cells provided an explanation for some of the clinical features of this disorder: the TH2 bias is likely to contribute to atopic disease, whereas defects in TH1 and TH17 cells compromise antiviral and antifungal immunity, respectively, explaining the infectious susceptibility of DOCK8-deficient patients."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.org/dc/terms/identifier"doi:10.1016/j.jaci.2016.07.016"xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Gray P."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Pillay B."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Casanova J.L."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Hambleton S."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Freeman A.F."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Su H.C."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Goodnow C.C."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Uzel G."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Phan T.G."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Ma C.S."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Tangye S.G."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Arkwright P.D."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Avery D.T."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Peake J."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Ziegler J.B."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Randall K.L."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Lugo Reyes S.O."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Smart J.M."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/author"Orange J."xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/date"2017"xsd:gYear
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/name"J Allergy Clin Immunol"xsd:string
http://purl.uniprot.org/citations/27554822http://purl.uniprot.org/core/pages"933-949"xsd:string
▶