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
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy