Partial DiGeorge syndrome (pDGS) can result from the silencing of a number of genes. One of genes, called CrkL (chicken tumor virus number 10 regulator of kinase like), plays a critical role in this disorder. Such silencing inhibits the function of natural killer cells (a component of immune system) that are important for controlling both virus-infected and tumor cells, said researchers led by those at Baylor College of Medicine in a report that appears on the Journal of Allergy and Clinical Immunology.
“We are the first to identify problems with natural killer cells in partial DiGeorge patients,” said Dr. Dongfang Liu, assistant professor of pediatrics – human immunobiology at Texas Children Hospital and Baylor College of Medicine. Previously, problems with the immune system’s T cells were recognized, but in this case researchers identified deficiencies in NK cells as well.
Other institutions involved in this study include Texas Children’s Hospital, Rice University and The University of Texas Health Science Center at Houston.
In this study, Liu and his colleagues studied the effect of silencing one of the CrkL genes found on chromosome 22 and found that the activity of natural killer cells was inhibited.
The problem occurs at the immunologic synapse – an interface between a NK and its susceptible target cell, said Liu.
Finding this required the use of super resolution microscopy, which allows capture of images at higher resolution than that of conventional light microscopy, said Liu.
“Scientists had mainly used this tool in basic research before this,” he said.
“We propose in this study that we can use the quality of immunologic synapse to study immunodeficiency,” he said. He anticipates that this technique could prove valuable in other types of immune deficiencies, such as primary deficiencies that are genetic and those that are acquired such as human immunodeficiency virus/AIDS.
Others who took part in this work include Peilin Zheng, Lenora M. Noroski, Imelda Celine Hanson, Yuhui Chen, Michelle Lee, Yu Huang, Michael X. Zhu, Pinaki Banerjee, George Makedonas, Jordan S. Orange and William T. Shearer.
Funding for this work came from Baylor–University of Texas at Houston Center for AIDS Research (Core Support Grant AI36211) from the National Institute of Allergy and Infectious Diseases, the Caroline Wiess Law Fund for Research in Molecular Medicine (Grant 2531319101), the Texas Children’s Hospital Pediatric Pilot Research Fund (Grant 2531319301), and the Lymphoma SPORE Developmental Research Program from Baylor College of Medicine and the Methodist Research Institute (Grants 2531319302 and P50 CA126752).