DOCK8 Expression in Regulatory T Cells Maintains their Stability and Limits Contact Hypersensitivity

Wilkie, Hazel; Janssen, Erin

doi:10.1016/j.jid.2020.09.027

Cited by 9 publications

(3 citation statements)

References 30 publications

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“…11 For example, the expression of DOCK8 in regulatory T cells (Tregs) limits contact hypersensitivity by fostering the stability and adaptability of Tregs in inflamed skin. 12 Additionally, the decreased expression level of DOCK8 and the abnormal signaling pathway driven by DOCK8 in autoimmune uveitis can promote the process of auto-reactive inflammation. 13 Nevertheless, the precise role of DOCK8 in regulating sepsis neutrophil immune function remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

“…DOCK8 is highly expressed in both B and T cells, and much research has focused on its role in the immune system 11 . For example, the expression of DOCK8 in regulatory T cells (Tregs) limits contact hypersensitivity by fostering the stability and adaptability of Tregs in inflamed skin 12 . Additionally, the decreased expression level of DOCK8 and the abnormal signaling pathway driven by DOCK8 in autoimmune uveitis can promote the process of auto‐reactive inflammation 13 .…”

Section: Introductionmentioning

confidence: 99%

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DOCK8 inhibits the immune function of neutrophils in sepsis by regulating aerobic glycolysis

Zhu,

Xu,

et al. 2023

Immunity Inflam & Disease

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IntroductionThis study endeavored to investigate the role of DOCK8 in modulating the immune function triggered by sepsis.MethodsExpression of DOCK8 in the whole blood of sepsis patients and its enrichment pathways were assayed by bioinformatics. Pearson analysis was used to predict the relationship between glycolytic signaling pathway and its relevance to neutrophil function in sepsis. A sepsis mouse model was then built by performing cecal ligation and puncture treatment on male mice. Neutrophils were isolated, and their purity was tested by flow cytometry. Neutrophils were then stimulated by lipopolysaccharide to build a sepsis cell model. Next, quantitative reverse transcription polymerase chain reaction and CCK‐8 were applied to test the expression of DOCK8 and cell viability, western blot to assay the expression of HK‐2, PKM2, and LDHA proteins, ELISA to measure the concentrations of TNF‐α, IL‐1β, and IL‐6, Transwell to detect the chemotaxis of neutrophils and flow cytometry to detect the phagocytic activity of neutrophils. Finally, in different treatment groups, we used Seahorse XF 96 to analyze the extracellular acidification rate (ECAR) of sepsis cells and used enzyme‐linked immunosorbent assay to detect the contents of pyruvic acid, lactic acid, and ATP in sepsis cells.ResultsDOCK8 was downregulated in sepsis blood and activated neutrophils. Aerobic glycolysis was positively correlated with sepsis. Activated neutrophils promoted the expression of inflammatory factors TNF‐α, IL‐1β, and IL‐6. Low expression of DOCK8 facilitated the proliferation, chemotaxis, and phagocytic activity of sepsis cells and promoted the expression of inflammatory factors. Bioinformatics analysis revealed that DOCK8 was enriched in the glycolytic signaling pathway. Low expression of DOCK8 induced ECAR, promoted the protein expression of HK‐2, PKM2 and LDHA, and favored the increase of pyruvate, lactate, and ATP contents. While 2‐DG treatment could restore these effects.ConclusionDOCK8 may inhibit sepsis‐induced neutrophil immune function by regulating aerobic glycolysis and causing excessive inflammation, which helps to explore potential therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

DOCK8 inhibits the immune function of neutrophils in sepsis by regulating aerobic glycolysis

Zhu,

Xu,

et al. 2023

Immunity Inflam & Disease

View full text Add to dashboard Cite

show abstract

“…3 Recently, defective Treg-cell function was shown to underlie this exaggerated T H 1 response. 10 Mice with inducible selective deficiency of DOCK8 in Treg cells, like Dock8 2/2 mice, demonstrated an exaggerated T H 1dominated CHS response to oxazolone with no evidence of T H 2 skewing. Moreover, adoptive transfer of Treg cells from WT mice, but not Dock8 2/2 mice, reversed the exaggerated CHS response of Dock8 2/2 recipients.…”

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confidence: 99%