Researchers discover a new gatekeeper controlling T cell release into the bloodstream

December 06, 2016

Oakland, CA (December 6, 2016) - A team of scientists led by Julie Saba, MD, PhD at UCSF Benioff Children's Hospital Oakland, has unveiled a novel role of thymic dendritic cells, which could result in new strategies to treat conditions such as autoimmune diseases, immune deficiencies, prematurity, infections, cancer, and the loss of immunity after bone marrow transplantation.

The study "Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress," appeared in the 'Journal of Experimental Medicine' (October 17, 2016 issue), published by Rockefeller University Press.

T lymphocytes are blood cells that carry out the main functions of our immune system. Dendritic cells and B lymphocytes are other types of immune cells that present foreign substances (such as microbial proteins) and "self" substances from our own tissues to T lymphocytes. In this way, T lymphocytes are "educated" to distinguish between self and non-self, so they can mount an immune response to pathogens but recognize and remain tolerant of one's own bodily tissues. When this system fails to operate properly, autoimmune disease and immune deficiencies can result.

T lymphocytes undergo maturation in the thymus, a small gland located just above the heart, and are then released into the bloodstream. T lymphocyte egress from the thymus is essential for immune surveillance and to fight various types of infections. Sphingosine-1-phosphate (S1P) is a lipid molecule found at high levels in the blood and low levels in most tissues. Mature T cells produce a cell surface receptor that recognizes S1P, allowing the S1P chemical gradient to attract them into the bloodstream once they have completed their education in the thymus. However, the precise mechanisms that control T lymphocyte egress are not fully understood.

Thymic dendritic cells have a well-established role in antigen presentation and immune tolerance in the body. In addition to this role, dendritic cells also act as metabolic gatekeepers of lymphocyte trafficking. The team showed that thymic dendritic cells take up S1P, a blood borne lipid mediator, and metabolize it through the actions of an enzyme called S1P lyase, generating a localized S1P gradient that facilitates T lymphocyte egress into the blood In light of the fact that dendritic cells are known to continually traffic throughout the body surveying for the presence of infectious agents, the team's observations raise the possibility that dendritic cells could potentially control the release of T lymphocytes in response to various disease states or conditions. These findings provide a deeper understanding of how the body regulates lymphocyte trafficking.

"T cells are needed to orchestrate the body's immune response against pathogenic organisms and also against cancer cells," says UCSF Benioff Oakland's Dr. Julie Saba, one of the study's authors. "In addition to natural T cells, genetically engineered T cells are being used in revolutionary ways to treat cancer. However, conditions such as chronic infection, aging, cancer and bone marrow transplantation can reduce T cell output from the thymus, compromising immune function. By learning what controls T cell output, we hope to be able to restore T cell production when it is low and provide more T cells for therapeutic purposes. "
-end-
In addition to Saba, other co-authors are Jesus Zamora-Pineda, Ashok Kumar, Jung H. Suh, and Meng Zhang,

The research is supported by the (CA129438) and Swim Across America funds (to J.D. Saba). Confocal images were acquired at the Children's Hospital Oakland Research Institute Microimaging Facility supported by an NIH grant (S10RR025472) and the Children's Hospital Branches, Inc. S1P measurements were obtained using the Children's Hospital Oakland Research Institute Mass Spectrometry Facility supported by an NIH Health grant (S10OD018070).

About UCSF Benioff Children's Hospital Oakland

UCSF Benioff Children's Hospital Oakland (formerly Children's Hospital & Research Center Oakland) is a premier, not-for-profit medical center for children in Northern California, and is the only hospital in the East Bay 100% devoted to pediatrics. UCSF Benioff Children's Hospital Oakland affiliated with UCSF Benioff Children's Hospital San Francisco on January 1, 2014. UCSF Benioff Children's Hospital Oakland is a national leader in many pediatric specialties including cardiology, hematology/oncology, neonatology, neurosurgery, endocrinology, urology, orthopedics, and sports medicine. The hospital is one of only five ACS Pediatric Level I Trauma Centers in the state, and has one of largest pediatric intensive care units in Northern California. UCSF Benioff Children's Hospital Oakland is also a leading teaching hospital with an outstanding pediatric residency program and a number of unique pediatric subspecialty fellowship programs.UCSF Benioff Children's Hospital Oakland's research arm, Children's Hospital Oakland Research Institute (CHORI), is internationally known for its basic and clinical research. CHORI is at the forefront of translating research into interventions for treating and preventing human diseases. CHORI has 250 members of its investigative staff, a budget of about $50 million, and is ranked among the nation's top ten research centers for National Institutes of Health funding to children's hospitals. For more information, go to http://www.childrenshospitaloakland.org and http://www.chori.org.

@UCSFBenioffOak

Children's Hospital & Research Center Oakland

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.