Publications

Publication Search

Search for publications by

DOCK8 is critical for the survival and function of NKT cells

Abstract

Patients with the DOCK8 immunodeficiency syndrome suffer from recurrent viral and bacterial infection, hyper-IgE 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, whilst in the liver, DOCK8-deficient NKT cells express reduced levels of the pro-survival factor Bcl-2 and the integrin LFA-1. Although the initial NKT cell response to antigen is intact in the absence of DOCK8, their ongoing proliferative and cytokine responses are impaired. Importantly, a similar defect in NKT cell numbers was detected in DOCK8-deficient humans, highlighting the relevance of the mouse model. In conclusion, our data demonstrate that DOCK8 is required for the development and survival of mature NKT cells, consistent with the idea that DOCK8 mediates survival signals within a specialised niche. Accordingly, impaired NKT cell numbers and function are likely to contribute to the susceptibility of DOCK8-deficient patients to recurrent infections and malignant disease.

Type Journal
Authors Crawford, G.; Enders, A.; Gileadi, U.; Stankovic, S.; Zhang, Q.; Lambe, T.; Crockford, T. L.; Lockstone, H. E.; Freeman, A.; Arkwright, P. D.; Smart, J. M.; Ma, C. S.; Tangye, S. G.; Goodnow, C. C.; Cerundolo, V.; Godfrey, D. I.; Su, H. C.; Randall, K. L.; Cornall, R. J.;
Publisher Name BLOOD
Published Date 2013-09-19 00:00:00
Published Volume 122
Published Issue 12
Published Pages 2052-61
URL http://www.ncbi.nlm.nih.gov/pubmed/23929855
Status Published