Labs around the world, and a core group at Penn, have been studying recently described populations of immune cells called innate lymphoid cells (ILCs). Some researchers liken them to foot soldiers that protect boundary tissues such as the skin, the lining of the lung, and the lining of the gut from microbial onslaught. They also have shown they play a role in inflammatory disease, when the body's immune system is too active.
In animal studies, group-2 innate lymphoid cells (ILC2s) confer immunity during a parasitic infection in mice and are also involved in allergic airway inflammation. A team of Perelman School of Medicine, researchers from the Departments of Medicine, Microbiology, Pathology and Laboratory Medicine, and Cancer Biology, found that maturation of ILC2s requires T-cell factor 1 (TCF-1, the product of the Tcf7 gene) to move forward. TCF-1 is protein that binds to specific parts of DNA to control transcription of genetic information from DNA to messenger RNA.
Avinash Bhandoola, PhD, professor of Pathology and Laboratory Medicine, and Qi Yang, PhD, a postdoc in the Bhandoola lab, describe in Immunity that one mechanism used to build ILCs is the same as that in T cells. Both cell types use a protein pathway centered on Notch that the lab of coauthor Warren Pear, MD, PhD, also in the Pathology and Laboratory Medicine, has studied for the last two decades. Other contributing authors are from the laboratory of David Artis, PhD in Microbiology, that are experts in ILC function, and Angela Haczku, MD, PhD, in the Department of Medicine, who focuses on asthma.
But what makes ILCs and T cells different in their final development? T cells are made in the thymus. ILCs don't need the thymus, but researchers don't know exactly where they are produced, just that the thymus isn't essential for their normal development, unlike T cells.
In the Immunity study, mice without the Tcf7 gene also lack ILC2, and were unable to mount an ILC2 immune response. Forced expression of TCF-1 in bone marrow progenitor cells in the mice partially bypassed the requirement for Notch signaling in the generation of ILC2 in the mice. The researchers suggest that transcription factors such as TCF-1 that underlie early steps of T cell development are also implicated in the development of innate lymphoid cells.
The collaborators' next steps are to better understand the basic steps of ILC development and build mouse models to test ILC function. "We want to know where ILCs develop in the body and what progenitor cells give rise to ILCs." says Bhandoola. "If we succeed in constructing mouse models missing different types of ILC, our collaborators can use them to better figure out what these cells do, and perhaps eventually how to control them."
This work was supported by National Institutes of Health Grants AI059621, AI098428, 5T32CA009140-38, T32CA-009140, DP5OD012116, R01AI047833, T32HD007516, 1F31CA165813, AI095466, AI095608, AI097333, and T32-AI007532.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.3 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 16 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $398 million awarded in the 2012 fiscal year.
The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania -- recognized as one of the nation's top "Honor Roll" hospitals by U.S. News & World Report; Penn Presbyterian Medical Center; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Penn Medicine also includes additional patient care facilities and services throughout the Philadelphia region.
Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2012, Penn Medicine provided $827 million to benefit our community.
Karen Kreeger | EurekAlert!
Unique genome architectures after fertilisation in single-cell embryos
30.03.2017 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
Transport of molecular motors into cilia
28.03.2017 | Aarhus University
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
30.03.2017 | Health and Medicine
30.03.2017 | Health and Medicine
30.03.2017 | Medical Engineering