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DOCK2-deficiency causes defects in anti-viral T cell responses and impaired control of herpes simplex virus infection.
Randall KL, Flesch IEA, Mei Y, Miosge LA, Aye R, Yu Z, Domaschenz H, Hollett NA, Russell TA, Stefanovic T, Wong YC, Seneviratne S, Ballard F, Hernandez Gallardo R, Croft SN, Goodnow CC, Bertram EM, Enders A, Tscharke DC. Randall KL, et al. J Infect Dis. 2024 Feb 15:jiae077. doi: 10.1093/infdis/jiae077. Online ahead of print. J Infect Dis. 2024. PMID: 38366567
DOCK2 Promotes Atherosclerosis by Mediating the Endothelial Cell Inflammatory Response.
Qian G, Adeyanju O, Cai D, Tucker TA, Idell S, Chen SY, Guo X. Qian G, et al. Am J Pathol. 2024 Apr;194(4):599-611. doi: 10.1016/j.ajpath.2023.09.015. Epub 2023 Oct 12. Am J Pathol. 2024. PMID: 37838011
In control mice and in humans, Dock2 was highly expressed in the ECs of atherosclerotic lesions. Dock2 deficiency was associated with attenuation of Icam-1, Vcam-1, and monocyte chemoattractant protein (Mcp)-1 in the aortic roots of mice fed HFD. ...
In control mice and in humans, Dock2 was highly expressed in the ECs of atherosclerotic lesions. Dock2 deficiency was associat …
DOCK2 Deficiency Attenuates Abdominal Aortic Aneurysm Formation-Brief Report.
Guo X, Cai D, Dong K, Li C, Xu Z, Chen SY. Guo X, et al. Arterioscler Thromb Vasc Biol. 2023 Jun;43(6):e210-e217. doi: 10.1161/ATVBAHA.122.318400. Epub 2023 Apr 6. Arterioscler Thromb Vasc Biol. 2023. PMID: 37021575
Accordingly, the elastin fragmentation observed in ApoE(-/-) mouse aorta infused with Ang II and elastase-treated aorta was significantly attenuated by DOCK2 deficiency. Moreover, DOCK2(-/-) decreased the prevalence and severity of aneurysm formation, as well as the …
Accordingly, the elastin fragmentation observed in ApoE(-/-) mouse aorta infused with Ang II and elastase-treated aorta was significantly at …
DOCK2 Promotes Asthma Development by Eliciting Airway Epithelial-Mesenchymal Transition.
Shi N, Zhang J, Chen SY. Shi N, et al. Am J Respir Cell Mol Biol. 2023 Sep;69(3):310-320. doi: 10.1165/rcmb.2022-0273OC. Am J Respir Cell Mol Biol. 2023. PMID: 36883952 Free PMC article.
Importantly, knockdown of DOCK2 inhibits, and overexpression of DOCK2 promotes, TGF-beta1-induced EMT. Consistently, DOCK2 deficiency suppresses the EMT of airway epithelium, attenuates the subepithelial fibrosis, and improves pulmonary function in HDM-induced asthm …
Importantly, knockdown of DOCK2 inhibits, and overexpression of DOCK2 promotes, TGF-beta1-induced EMT. Consistently, DOCK2 deficie …
DOCK2 contributes to pulmonary fibrosis by promoting lung fibroblast to myofibroblast transition.
Guo X, Adeyanju O, Sunil C, Mandlem V, Olajuyin A, Huang S, Chen SY, Idell S, Tucker TA, Qian G. Guo X, et al. Am J Physiol Cell Physiol. 2022 Jul 1;323(1):C133-C144. doi: 10.1152/ajpcell.00067.2022. Epub 2022 May 18. Am J Physiol Cell Physiol. 2022. PMID: 35584329 Free PMC article.
Furthermore, increased lung DOCK2 expression colocalized with the FMT marker alpha-SMA in the bleomycin-induced pulmonary fibrosis model, implicating DOCK2 in the regulation of lung fibroblast phenotypic changes. Importantly, DOCK2 deficiency also attenuated bleomyc …
Furthermore, increased lung DOCK2 expression colocalized with the FMT marker alpha-SMA in the bleomycin-induced pulmonary fibrosis model, im …
Hematopoietic stem cell transplantation complicated with EBV associated hemophagocytic lymphohistiocytosis in a patient with DOCK2 deficiency.
Aytekin ES, Çağdaş D, Tan Ç, Çavdarlı B, Bilgiç I, Tezcan İ. Aytekin ES, et al. Turk J Pediatr. 2021;63(6):1072-1077. doi: 10.24953/turkjped.2021.06.016. Turk J Pediatr. 2021. PMID: 35023658 Free article.
In DOCK2 deficiency; T, B and NK cell numbers are decreased and functions are impaired resulting in severe atrophy of secondary lymphoid tissues. ...CONCLUSIONS: Genetic testing is necessery for early diagnosis of DOCK2 deficiency. The curative treatme …
In DOCK2 deficiency; T, B and NK cell numbers are decreased and functions are impaired resulting in severe atrophy of secondar …
First patient in the Iranian Registry with novel DOCK2 gene mutation, presenting with skeletal tuberculosis, and review of literature.
Sharifinejad N, Sadri H, Kalantari A, Delavari S, Noohi A, Aminpour Y, Sabzevari A, Azizi G. Sharifinejad N, et al. Allergy Asthma Clin Immunol. 2021 Dec 6;17(1):126. doi: 10.1186/s13223-021-00631-5. Allergy Asthma Clin Immunol. 2021. PMID: 34872585 Free PMC article.
BACKGROUND: Dedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral immunological abnormalities leading to early-onset infections. ...CONCLUSION: DOCK2 deficiency should be considered in the co …
BACKGROUND: Dedicator of cytokinesis 2 (DOCK2) deficiency is an inborn error of immunity characterized by cellular and humoral …
Investigating the Variation of TREC/KREC in Combined Immunodeficiencies.
Shakerian L, Nourizadeh M, Badalzadeh M, Fazlollahi MR, Shokouhi Shoormasti R, Saghafi S, Esmaeili B, Alizadeh Z, Borte S, Houshmand M, Hammarström L, Pourpak Z. Shakerian L, et al. Iran J Allergy Asthma Immunol. 2021 Aug 7;20(4):402-412. Iran J Allergy Asthma Immunol. 2021. PMID: 34418894 Free article.
Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 with DOCK8 deficiency, 4 with signal transducer and activator of transcription 3 (STAT3) deficiency, and 8 children with unknown genetic defe …
Patients had a final diagnosis of common variable immunodeficiency (n=23), ataxia-telangiectasia (AT) (n=17), hyper-IgE syndrome (HIES) (7 w …
Dedicator of cytokinesis protein 2 couples with lymphoid enhancer-binding factor 1 to regulate expression of CD21 and B-cell differentiation.
Jing Y, Kang D, Liu L, Huang H, Chen A, Yang L, Jiang P, Li N, Miller H, Liu Z, Zhu X, Yang J, Wang X, Sun J, Liu Z, Liu W, Zhou X, Liu C. Jing Y, et al. J Allergy Clin Immunol. 2019 Nov;144(5):1377-1390.e4. doi: 10.1016/j.jaci.2019.05.041. Epub 2019 Aug 9. J Allergy Clin Immunol. 2019. PMID: 31405607
RESULTS: We found that the absence of DOCK2 led to downregulation of proximal and distal BCR signaling molecules, including CD19, but upregulation of SH2-containing inositol 5 phosphatase 1, a negative signaling molecule. Interestingly, DOCK2 deficiency reduced CD19 …
RESULTS: We found that the absence of DOCK2 led to downregulation of proximal and distal BCR signaling molecules, including CD19, but upregu …
Human DOCK2 Deficiency: Report of a Novel Mutation and Evidence for Neutrophil Dysfunction.
Moens L, Gouwy M, Bosch B, Pastukhov O, Nieto-Patlàn A, Siler U, Bucciol G, Mekahli D, Vermeulen F, Desmet L, Maebe S, Flipts H, Corveleyn A, Moshous D, Philippet P, Tangye SG, Boisson B, Casanova JL, Florkin B, Struyf S, Reichenbach J, Bustamante J, Notarangelo LD, Meyts I. Moens L, et al. J Clin Immunol. 2019 Apr;39(3):298-308. doi: 10.1007/s10875-019-00603-w. Epub 2019 Mar 5. J Clin Immunol. 2019. PMID: 30838481 Free PMC article.
Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency. Here, we describe a new kindred with four affected siblings harboring a homozygous splice-site mutation (c.2704-2 A > C) in DOCK2. ...
Until now, the function of phagocytes, specifically neutrophils, has not been assessed in human DOCK2 deficiency. Here, we des …
DOCK2 Deficiency in a Patient with Hyper IgM Phenotype.
Alizadeh Z, Mazinani M, Shakerian L, Nabavi M, Fazlollahi MR. Alizadeh Z, et al. J Clin Immunol. 2018 Jan;38(1):10-12. doi: 10.1007/s10875-017-0468-5. Epub 2017 Dec 4. J Clin Immunol. 2018. PMID: 29204803 No abstract available.
Growth of B Cell Receptor Microclusters Is Regulated by PIP2 and PIP3 Equilibrium and Dock2 Recruitment and Activation.
Wang J, Xu L, Shaheen S, Liu S, Zheng W, Sun X, Li Z, Liu W. Wang J, et al. Cell Rep. 2017 Nov 28;21(9):2541-2557. doi: 10.1016/j.celrep.2017.10.117. Cell Rep. 2017. PMID: 29186690 Free article.
Mechanistically, we find that PIP(3)-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for the sustained growth of BCR microclusters through remodeling of the F-actin cytoskeleton. As a consequence, Dock2 deficiency sig …
Mechanistically, we find that PIP(3)-dependent recruitment and activation of a guanine nucleotide exchange factor, Dock2, is required for th …
DOCK2 deficiency mitigates HFD-induced obesity by reducing adipose tissue inflammation and increasing energy expenditure.
Guo X, Li F, Xu Z, Yin A, Yin H, Li C, Chen SY. Guo X, et al. J Lipid Res. 2017 Sep;58(9):1777-1784. doi: 10.1194/jlr.M073049. Epub 2017 Jul 17. J Lipid Res. 2017. PMID: 28716822 Free PMC article.
DOCK2(-/-) mice with HFD showed decreased body weight gain and improved metabolic homeostasis and insulin resistance compared with WT mice. DOCK2 deficiency also attenuated adipose tissue and systemic inflammation accompanied by reduced macrophage infiltration. ...M …
DOCK2(-/-) mice with HFD showed decreased body weight gain and improved metabolic homeostasis and insulin resistance compared with WT mice. …
DOCK8 deficiency: Insights into pathophysiology, clinical features and management.
Biggs CM, Keles S, Chatila TA. Biggs CM, et al. Clin Immunol. 2017 Aug;181:75-82. doi: 10.1016/j.clim.2017.06.003. Epub 2017 Jun 15. Clin Immunol. 2017. PMID: 28625885 Free PMC article. Review.
It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the emerging spectrum of PIDs resulting from DOCK protein family abnormalities....
It also surveys the recently discovered combined immunodeficiency due to DOCK2 deficiency, highlighting in the process the eme …
Current Status of Dedicator of Cytokinesis-Associated Immunodeficiency: DOCK8 and DOCK2.
Dimitrova D, Freeman AF. Dimitrova D, et al. Dermatol Clin. 2017 Jan;35(1):11-19. doi: 10.1016/j.det.2016.07.002. Dermatol Clin. 2017. PMID: 27890234 Free PMC article. Review.
Early hematopoietic stem cell transplantation is gaining prominence as a definitive treatment given the potential for severe complications and mortality in this disease. Recently, DOCK2 deficiency has been identified in several patients with early-onset invasive bac …
Early hematopoietic stem cell transplantation is gaining prominence as a definitive treatment given the potential for severe complications a …
Striking Immune Phenotypes in Gene-Targeted Mice Are Driven by a Copy-Number Variant Originating from a Commercially Available C57BL/6 Strain.
Mahajan VS, Demissie E, Mattoo H, Viswanadham V, Varki A, Morris R, Pillai S. Mahajan VS, et al. Cell Rep. 2016 May 31;15(9):1901-9. doi: 10.1016/j.celrep.2016.04.080. Epub 2016 May 19. Cell Rep. 2016. PMID: 27210752 Free PMC article.
This particular commercially obtained subline of C57BL/6 mice also exhibits several striking immune phenotypes that have been previously described in the context of Dock2 deficiency. Inadvertent backcrossing of a number of gene-targeted mice into this background has …
This particular commercially obtained subline of C57BL/6 mice also exhibits several striking immune phenotypes that have been previously des …
Inherited DOCK2 Deficiency in Patients with Early-Onset Invasive Infections.
Dobbs K, Domínguez Conde C, Zhang SY, Parolini S, Audry M, Chou J, Haapaniemi E, Keles S, Bilic I, Okada S, Massaad MJ, Rounioja S, Alwahadneh AM, Serwas NK, Capuder K, Çiftçi E, Felgentreff K, Ohsumi TK, Pedergnana V, Boisson B, Haskoloğlu Ş, Ensari A, Schuster M, Moretta A, Itan Y, Patrizi O, Rozenberg F, Lebon P, Saarela J, Knip M, Petrovski S, Goldstein DB, Parrott RE, Savas B, Schambach A, Tabellini G, Bock C, Chatila TA, Comeau AM, Geha RS, Abel L, Buckley RH, İkincioğulları A, Al-Herz W, Helminen M, Doğu F, Casanova JL, Boztuğ K, Notarangelo LD. Dobbs K, et al. N Engl J Med. 2015 Jun 18;372(25):2409-22. doi: 10.1056/NEJMoa1413462. N Engl J Med. 2015. PMID: 26083206 Free PMC article.
Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were normalized by treatment with interferon alfa-2b or after expression of wild-type DOCK2. Conclusions Autosomal recessive DOCK2 defic …
Moreover, in DOCK2-deficient fibroblasts, viral replication was increased and virus-induced cell death was enhanced; these conditions were n …
Dedicator of cytokinesis 2, a novel regulator for smooth muscle phenotypic modulation and vascular remodeling.
Guo X, Shi N, Cui XB, Wang JN, Fukui Y, Chen SY. Guo X, et al. Circ Res. 2015 May 8;116(10):e71-80. doi: 10.1161/CIRCRESAHA.116.305863. Epub 2015 Mar 18. Circ Res. 2015. PMID: 25788409 Free PMC article.
METHODS AND RESULTS: Platelet-derived growth factor-BB induced DOCK2 expression while modulating SMC phenotype. DOCK2 deficiency diminishes platelet-derived growth factor-BB or serum-induced downregulation of SMC markers. ...
METHODS AND RESULTS: Platelet-derived growth factor-BB induced DOCK2 expression while modulating SMC phenotype. DOCK2 deficiency …
DOCK2 and DOCK5 act additively in neutrophils to regulate chemotaxis, superoxide production, and extracellular trap formation.
Watanabe M, Terasawa M, Miyano K, Yanagihara T, Uruno T, Sanematsu F, Nishikimi A, Côté JF, Sumimoto H, Fukui Y. Watanabe M, et al. J Immunol. 2014 Dec 1;193(11):5660-7. doi: 10.4049/jimmunol.1400885. Epub 2014 Oct 22. J Immunol. 2014. PMID: 25339677 Free PMC article.
DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major regulators of Rac in neutrophils. However, because DOCK2 deficiency does not completely abolish fMLF-induced Rac activation, other Rac GEFs may also participate in this process. ...
DOCK2, an atypical guanine nucleotide exchange factor (GEF), is one of the major regulators of Rac in neutrophils. However, because DOCK2 …
Interferon regulatory factor-5 deficiency ameliorates disease severity in the MRL/lpr mouse model of lupus in the absence of a mutation in DOCK2.
Yasuda K, Watkins AA, Kochar GS, Wilson GE, Laskow B, Richez C, Bonegio RG, Rifkin IR. Yasuda K, et al. PLoS One. 2014 Jul 30;9(7):e103478. doi: 10.1371/journal.pone.0103478. eCollection 2014. PLoS One. 2014. PMID: 25076492 Free PMC article.
As DOCK2 regulates lymphocyte trafficking and Toll-like receptor signaling, this raised the possibility that some of the protective effects attributed to IRF5 deficiency in the mouse lupus models may instead have been due to DOCK2 deficiency. We have therefore here …
As DOCK2 regulates lymphocyte trafficking and Toll-like receptor signaling, this raised the possibility that some of the protective effects …
The Rac activator DOCK2 regulates natural killer cell-mediated cytotoxicity in mice through the lytic synapse formation.
Sakai Y, Tanaka Y, Yanagihara T, Watanabe M, Duan X, Terasawa M, Nishikimi A, Sanematsu F, Fukui Y. Sakai Y, et al. Blood. 2013 Jul 18;122(3):386-93. doi: 10.1182/blood-2012-12-475897. Epub 2013 May 29. Blood. 2013. PMID: 23719299 Free article.
Here, we show that DOCK2, an atypical guanine nucleotide exchange factor for Rac, plays a key role in NK cell-mediated cytotoxicity. We found that although DOCK2 deficiency in NK cells did not affect conjugate formation with target cells, DOCK2-deficienct NK cells f …
Here, we show that DOCK2, an atypical guanine nucleotide exchange factor for Rac, plays a key role in NK cell-mediated cytotoxicity. We foun …
Differential requirement for DOCK2 in migration of plasmacytoid dendritic cells versus myeloid dendritic cells.
Gotoh K, Tanaka Y, Nishikimi A, Inayoshi A, Enjoji M, Takayanagi R, Sasazuki T, Fukui Y. Gotoh K, et al. Blood. 2008 Mar 15;111(6):2973-6. doi: 10.1182/blood-2007-09-112169. Epub 2008 Jan 15. Blood. 2008. PMID: 18198348 Free article.
Here we show that DOCK2, a hematopoietic cell-specific CDM family protein, is indispensable for migration of plasmacytoid DCs (pDCs), but not myeloid DCs (mDCs). Although DOCK2-deficiency did not affect development of pDCs, DOCK2-deficient (DOCK2(-/-)) mice exhibite …
Here we show that DOCK2, a hematopoietic cell-specific CDM family protein, is indispensable for migration of plasmacytoid DCs (pDCs), but no …
DOCK2 is required in T cell precursors for development of Valpha14 NK T cells.
Kunisaki Y, Tanaka Y, Sanui T, Inayoshi A, Noda M, Nakayama T, Harada M, Taniguchi M, Sasazuki T, Fukui Y. Kunisaki Y, et al. J Immunol. 2006 Apr 15;176(8):4640-5. doi: 10.4049/jimmunol.176.8.4640. J Immunol. 2006. PMID: 16585555
DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster myoblast city, is critical for lymphocyte migration and regulates T cell responsiveness through immunological synapse formation, yet its role in Valpha14 NKT cells remains unknown. We found tha …
DOCK2, a mammalian homolog of Caenorhabditis elegans CED-5 and Drosophila melanogaster myoblast city, is critical for lymphocyte migration a …
Deletion of DOCK2, a regulator of the actin cytoskeleton in lymphocytes, suppresses cardiac allograft rejection.
Jiang H, Pan F, Erickson LM, Jang MS, Sanui T, Kunisaki Y, Sasazuki T, Kobayashi M, Fukui Y. Jiang H, et al. J Exp Med. 2005 Oct 17;202(8):1121-30. doi: 10.1084/jem.20050911. J Exp Med. 2005. PMID: 16230477 Free PMC article.
DOCK2 plays a critical role in lymphocyte homing and immunological synapse formation by regulating the actin cytoskeleton, yet its role in the in vivo immune response remains unknown. We show here that DOCK2 deficiency enables long-term survival of cardiac allograft …
DOCK2 plays a critical role in lymphocyte homing and immunological synapse formation by regulating the actin cytoskeleton, yet its role in t …