Journal article

DOCK8 is critical for the survival and function of NKT cells

Greg Crawford, Anselm Enders, Uzi Gileadi, Sanda Stankovic, Qian Zhang, Teresa Lambe, Tanya L Crockford, Helen E Lockstone, Alexandra Freeman, Peter D Arkwright, Joanne M Smart, Cindy S Ma, Stuart G Tangye, Christopher C Goodnow, Vincenzo Cerundolo, Dale I Godfrey, Helen C Su, Katrina L Randall, Richard J Cornall

BLOOD | AMER SOC HEMATOLOGY | Published : 2013

Abstract

Patients with the dedicator of cytokinesis 8 (DOCK8) immunodeficiency syndrome suffer from recurrent viral and bacterial infections, hyper-immunoglobulin E levels, eczema, and greater susceptibility to cancer. Because natural killer T (NKT) cells have been implicated in these diseases, we asked if these cells were affected by DOCK8 deficiency. Using a mouse model, we found that DOCK8 deficiency resulted in impaired NKT cell development, principally affecting the formation and survival of long-lived, differentiated NKT cells. In the thymus, DOCK8-deficient mice lack a terminally differentiated subset of NK1.1(+) NKT cells expressing the integrin CD103, whereas in the liver, DOCK8-deficient NK..

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Grants

Awarded by NHMRC


Awarded by Medical Research Council


Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES


Funding Acknowledgements

This work was supported by the Medical Research Council, National Institute for Health Research Biomedical Research Centre Program, National Institutes of Medical Research, Australian National Health and Medical Research Council (NHMRC), and the Intramural Research Program of the National Institutes of Health, National Institute of Allergy and Infectious Diseases. The authors acknowledge the following personal awards: Medical Research Council Centenary Early Career Award (to G.C.), NHMRC Career Development Fellowship (to A. E.), NHMRC Senior Principal Research Fellowship (to D. I. G.), NHMRC Career Development Fellowship (to C. S. M.), NHMRC grant GNT1022922 (to K. L. R.), and NHMRC Principal Research Fellowship (to S.G.T.).