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DOCK8 regulates signal transduction events to control immunity

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Abstract

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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Authors and Affiliations

  1. Cancer Immunology Division, Immune Defence Laboratory, The Peter MacCallum Cancer Centre, East Melbourne, 3002, Victoria, Australia

    Conor J Kearney & Jane Oliaro

  2. Sir Peter MacCallum Department of Oncology, The University of Melbourne, Parkville, 3052, Victoria, Australia

    Conor J Kearney & Jane Oliaro

  3. Department of Immunology and Infectious Disease, The John Curtin School of Medical Research, Australian National University, Acton, Australian Capital Territory 2601, Australia

    Katrina L Randall

  4. Australian National University Medical School, Australian National University, Acton, Australian Capital Territory 2605, Australia

    Katrina L Randall

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  1. Conor J Kearney
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  2. Katrina L Randall
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  3. Jane Oliaro
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Correspondence to Jane Oliaro.

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Kearney, C., Randall, K. & Oliaro, J. DOCK8 regulates signal transduction events to control immunity. Cell Mol Immunol 14, 406–411 (2017). https://doi.org/10.1038/cmi.2017.9

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