St. Jude Children’s Research Hospital investigators have identified a signaling molecule that functions like a factory supervisor to ensure that the right mix of specialized T cells is available to fight infections and guard against autoimmune disease.
The research also showed the molecule, phosphatase MKP-1, is an important regulator of immune balance. Working in laboratory cell lines and mice with specially engineered immune systems, scientists demonstrated that MKP-1 serves as a bridge between the innate immune response that is the body’s first line of defense against infection and the more specialized adaptive immune response that follows. The results are published in the July 22 print edition of the scientific journal Immunity.
The results raise hopes that the MKP-1 pathway will lead to new tools for shaping the immune response, said Hongbo Chi, Ph.D., assistant member of the St. Jude Department of Immunology and the study’s senior author. The co-first authors are Gonghua Huang, Ph.D., and Yanyan Wang, Ph.D., both postdoctoral fellows in Chi’s laboratory.
The findings provide new details about how dendritic cells regulate the fate of naïve or undifferentiated T cells. Dendritic cells are the sentinels of the innate immune response, patrolling the body and ready to respond at the first sign of infection.
Investigators were surprised that a single molecule regulated production of three out of the four major subsets of T cells, which each play different roles. MKP-1 is a negative regulator of the enzyme p38, which is part of the MAP kinase family of enzymes that control pathways involved in cell proliferation, differentiation and death.
Chi and his colleagues demonstrated that MKP-1 works in dendritic cells by altering production of protein messengers known as cytokines. Those cytokines determine which subset of specialized T cells the undifferentiated T cells are fated to become. In this study, scientists showed that MKP1 controls production of the cytokines that yield T helper 1 (Th1), T helper 17 (Th17) and regulatory T (Treg) cells. Th1 cells combat intracellular bacterial and viral infections. Th17 cells fight extracellular bacterial infections and fungi. Treg cells help with immune suppression, protecting against autoimmune diseases.
The study showed that suppression of p38 by MKP-1 promotes production of interleukin 12 (IL-12), which leads to an increase in Th1 cells. Rising IL-12 coincides with a drop in interleukin 6 (IL-6) and a corresponding dip in production of Th17. MKP-1 also inhibited the generation of Treg cells by down-regulating production of a third cytokine, TGF-beta.
Knocking out MKP-1 in mice disrupted production of IL-12 and IL-6 in dendritic cells as well as the anti-bacterial and anti-fungal immune response, researchers reported. MKP-1 deficiency also promoted T-cell driven inflammation in a mouse model of colitis, an inflammatory disease.
“MKP-1 is the first signaling molecule found in dendritic cells to program differentiation of these diverse T- cell subsets,” Chi said.
Previous work by other scientists focused on T cell differentiation in response to stimulation by cytokines. “This research fills a gap in our understanding of dendritic cell-mediated control of T-cell lineage choices,” Chi said. “T cells do not recognize pathogens directly, but dendritic cells do. T cells need dendritic cells to tell them what to do. In this study, we show that MKP-1 signaling in dendritic cells bridges the innate and adaptive immune responses by regulating cytokine production.”
Other authors are Lewis Shi and Thirumala-Devi Kanneganti, both of St. Jude.
The research was supported in part by the National Institutes of Health, the National Multiple Sclerosis Society, the Cancer Research Institute, The Hartwell Foundation and ALSAC.St. Jude Children’s Research Hospital
Founded in 1962 by the late entertainer Danny Thomas, St. Jude freely shares its discoveries with scientific and medical communities around the world, publishing more research articles than any other pediatric cancer research center in the United States. St. Jude treats more than 5,700 patients each year and is the only pediatric cancer research center where families never pay for treatment not covered by insurance. St. Jude is financially supported by thousands of individual donors, organizations and corporations without which the hospital’s work would not be possible. For more information, go to www.stjude.org.
Summer Freeman | Newswise Science News
Further reports about: > Balanced > CHI > Cancer > IL-12 > Immune cell activation > MKP-1 > Molecule > T cells > T-cell > TH1 > TH17 > TREG > autoimmune disease > bacterial infection > cancer research > dendritic cells > identified > immune response > immune system > signaling molecule > viral infection
20.11.2017 | Washington University in St. Louis
Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign
The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.
Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...
Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.
That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...
Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.
During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....
The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.
Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...
Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...
15.11.2017 | Event News
15.11.2017 | Event News
30.10.2017 | Event News
20.11.2017 | Earth Sciences
20.11.2017 | Earth Sciences
20.11.2017 | Life Sciences