DOCK8 regulates signal transduction events to control immunity
Open accessAbstract
Genetic mutations in the gene encoding DOCK8 cause an autosomal recessive form of hyper immunoglobulin E syndrome (AR-HIES), referred to as DOCK8 deficiency. DOCK8 deficiency in humans results in the onset of combined immunodeficiency disease (CID), clinically associated with chronic infections with diverse microbial pathogens, and a predisposition to malignancy. It is now becoming clear that DOCK8 regulates the function of diverse immune cell sub-types, particularly lymphocytes, to drive both innate and adaptive immune responses. Early studies demonstrated that DOCK8 is required for lymphocyte survival, migration and immune synapse formation, which translates to poor pathogen control in the absence of DOCK8. However, more recent advances have pointed to a crucial role for DOCK8 in regulating the signal transduction events that control transcriptional activity, cytokine production and functional polarization of immune cells. Here, we summarize recent advances in our understanding of DOCK8 function, paying particular attention to an emerging role as a signaling intermediate to promote immune responses to diverse external stimuli.
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Patients with large deletions in the DOCK8 gene have increased susceptibility to pathogenic infections and exhibit allergic diseases.
“In line with this, patients with large deletions in the DOCK8 gene experience increased susceptibility to pathogenic infections yet also exhibit allergic diseases, leading to great interest surrounding DOCK8 in the field of immunology, which has recently been reviewed in great detail (50, 115, 116).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [116]
The Introduction and Table 1 report that patients with DOCK8 deficiency have recurrent infections, eczema, and food allergy. The paper describes loss-of-function mutations generally, but does not establish that these manifestations occur specifically in patients with large DOCK8 deletions. (LLM, conf=0.85)
Experimental — accuracy not yet measuredMutations in the DOCK8 gene are associated with autism disorders.
“Mutations in the DOCK8 gene have also been associated with autism disorders (116).”
From RHO to the DOCK for GDP disembarking: Structural insights into the DOCK GTPase nucleotide exchange factors (2021) · cites this paper as [116]
The Introduction links DOCK8 mutations to combined immunodeficiency, and the Conclusion discusses their effects on immune function. Neither passage addresses autism; searches for autism and related neurodevelopmental terms found no supporting passage in our copy. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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“In line with this, patients with large deletions in the DOCK8 gene experience increased susceptibility to pathogenic infections yet also exhibit allergic diseases, leading to great interest surrounding DOCK8 in the field of immunology, which has recently been reviewed in great detail (50, 115, 116).”
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Identifying Tipping Points during Healthy Brain Aging through Single‐Nucleus Transcriptomic Analysis
Wu, P., Zhao, X., Chen, Z., Huang, J., Dai, T., Zhou, J., Xiao, L., Chen, L., Zhao, R. C., & Wang, J. (2025) · Advanced Science · doi:10.1002/advs.202505779 · Cited by 6 · see citing works
dock8 deficiency attenuates microglia colonization in early zebrafish larvae
Wu, L., Xue, R., Chen, J., & Xu, J. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01155-6 · Cited by 4 · see citing works
DOCK8 is essential for neutrophil mediated clearance of cutaneous S. aureus infection
Wilkie, H., Timilshina, M., Rahmayanti, S., Das, M., Pelovitz, T., & Geha, R. S. (2023) · Clinical Immunology · doi:10.1016/j.clim.2023.109681 · Cited by 4 · see citing works
Global coordination of protrusive forces in migrating immune cellsPreprint
Reis-Rodrigues, P., Čanigová, N., Avellaneda, M. J., Gaertner, F., Vaahtomeri, K., Riedl, M., Merrin, J., Hauschild, R., Fukui, Y., Garcia, A. J., et al. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.07.26.605242 · Cited by 4 · see citing works
Gennery, A. R., & Albert, M. H. (2025) · Current Opinion in Allergy and Clinical Immunology · doi:10.1097/aci.0000000000001115 · Cited by 3 · see citing works
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New Gene Variants Associated with the Risk of Chronic HBV Infection
Fan, M., Wang, J., Wang, S., Li, T., Pan, H., Liu, H., Xu, H., Zhernakova, D. V., O’Brien, S. J., Feng, Z., et al. (2020) · Virologica Sinica · doi:10.1007/s12250-020-00200-x · Cited by 3 · see citing works
Dock8 regulates Th2 cell differentiation through ANXA1
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Structure and Signalling Function of the B-Cell Antigen Receptor and Its Coreceptors
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DOCK8 Mutation in Patient with Juvenile Idiopathic Arthritis and Sjögren’s Syndrome
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Li, Y., Song, L., Xu, Y., Chi, Y., Hu, Y., Wang, J., Robeldo, D., Mukiibi, R., & Chen, S. (2025) · Fish & Shellfish Immunology · doi:10.1016/j.fsi.2025.110145 · Cited by 2 · see citing works
Inmunodeficiencia combinada debida a deficiencia de DOCK8. Lo que sabemos hasta ahora
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MDA5 regulates BCR signaling and B-cell function via NF-κB-mediated DNM1
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Primary atopic disorders: Monogenic insights into immunity
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DOCK8 in immune cells: roles and mechanisms
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IPEX Syndrome and IPEX-Related Disorders
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Candidiasi mucocutanea cronica: quando sospettarla, come diagnosticarla e trattarla
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CAR-Cytotox: A Standardized Framework to Quantify Cytotoxic Potency in CAR T Cell ProductsPreprint
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Hepatic γδ NKT cells modulate liver-resident CD8+ T cells to attenuated malaria parasite vaccinesPreprint
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- Authors
- Kearney, C. J., Randall, K. L., & Oliaro, J.
- Affiliations
- The University of Melbourne (AU)
- Australian National University (AU)
- Corresponding author
- Oliaro, Jane
- Venue
- Cellular & Molecular Immunology
- Published
- 2017-04-03
- Volume
- 14
- Issue
- 5
- Pages
- 406-411
- ISSN
- 1672-7681 (ISSN-L)
- 2042-0226
- PMC
- PMC5423093
- OpenAlex
- W2604456522
- Cited by
- 70
- References
- 44
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 8 · 2023: 8 · 2022: 11 · 2021: 14 · 2020: 8 · 2019: 2 · 2018: 2 · 2017: 1
- FWCI
- 0.37
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Cellular and Molecular Immunology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunodeficiency and Autoimmune Disorders
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Blood disorders and treatments
- Keywords
- DOCK8, DOCK8 deficiency, combined immunodeficiency, signal transduction, lymphocyte signaling, immunological synapse, lymphocyte migration, lymphocyte survival, cytokine production, immune cell polarization, innate immunity, adaptive immunity, chronic infection, malignancy predisposition
- MeSH terms
- Humans, Immunity, Cellular, Infections, Signal Transduction, Guanine Nucleotide Exchange Factors
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