Previously unknown immune cell may help those with Crohn's and colitis

November 04, 2008

The tonsils and lymphoid tissues in the intestinal tract that help protect the body from external pathogens are the home base of a rare immune cell newly identified by researchers at Washington University School of Medicine in St. Louis. The researchers indicate that the immune cells could have a therapeutic role in inflammatory bowel diseases (IBD) such as Crohn's disease and ulcerative colitis.

Their report will appear in an upcoming issue of the journal Nature and is currently available through advanced online publication.

"These cells have an anti-inflammatory effect," says the article's lead author Marina Cella, M.D., research associate professor of pathology and immunology. "In the gut, we have beneficial bacteria, and it's important that the body does not recognize them as something detrimental and start an inflammatory reaction, which could ultimately promote tissue damage and inflammatory or autoimmune diseases such as IBD. The cells we've discovered are important for keeping such harmful inflammatory processes in check."

The cells are a type of natural killer (NK) cells, which are white blood cells classically known to eliminate tumor cells and cells infected by viruses. Because of their killer tendencies, NK cells are carefully controlled and don't act until they receive the right signal.

Some of the signals that activate the newly discovered cells are the same signals that turn on a different immune cell with strong inflammatory properties that can promote cell death and tissue damage if chronically active. But the anti-inflammatory cells, termed NK-22 cells, that the Washington University researchers discovered have the opposite effect - they promote cell proliferation and wound healing.

"That finding suggests that these cells play a role in maintaining a balance in the immune system between inflammatory processes and anti-inflammatory processes," says coauthor Jason Mills, M.D., Ph.D., assistant professor of pathology and immunology and of developmental biology. "They make sure that factors that turn up inflammation can be counteracted by the coordinated activation of anti-inflammatory effects."

The NK-22 cells are part of the innate immune system, which reacts quickly to invading pathogens. The researchers found that in response to immune signals warning of foreign invaders, the cells produce copious quantities of a compound called IL-22, which is why the researchers chose to name them NK-22 cells.

"NK-22 cells are already present in the mucosal tissue of the gastrointestinal tract, and as soon as they see a pathogen, they react," Cella says. "That is a great advantage to the body because it produces a protective response in the very first hours of pathogenic attack."

Now that immunologists know NK-22 cells exist and what immune factors influence them, they may be able to capitalize on them to treat a variety of inflammatory diseases, the researchers say.

"Diseases such as inflammatory bowel disease result from a defect in the intestine's protective barrier," says senior author Marco Colonna, M.D., professor of pathology and immunology. "If we can develop methods to culture NK-22 cells, we may be able to use them to promote healing and protect the gastrointestinal tract."

Washington University School of Medicine

Guide to Signal Pathways in Immune Cells
by E. Nigel Wardle (Author)

In Guide to Signal Pathways in Immune Cells, Nigel E. Wardle presents vital information in regards to white cells, like the neutrophils and macrophages, T and B lymphocytes, natural killer cells and mast cells, as they constitute the immune defenses against microbial invaders or tumor cells. In all such cells the necessary information processing for their activities utilizes a network of intracellular signaling pathways. As a guide this book aims to extend understanding of the basic signal transduction pathways that will be suitable for students of immunology or cell biology and for medical personnel at all levels.

Primer to the Immune Response: Academic Cell Update Edition
by Tak W. Mak (Author), Mary Saunders (Author)

Now available with the most current and relevant research from Cell Press, Mak's Primer to the Immune Response, Academic Cell Update Edition, gives readers both the concepts and the applications students need to know to fully grasp Immunology. Mak introduces basic concepts and then follows with specific applications in research today. This book is further enhanced by its inclusion in the Academic Cell collaboration, providing it with links to current and recently published research.Now with an online study guide with the most current, relevant research from Cell PressFull supplements including test bank, powerpoint and online self quizzingColor illustrations enhance key topics and concepts

Mechanisms of Lymphocyte Activation and Immune Regulation XI: B Cell Biology (Advances in Experimental Medicine and Biology) (v. 11)
by Sudhir Gupta (Editor), Frederick W. Alt (Editor), Max D. Cooper (Editor), Fritz Melchers (Editor), Klaus Rajewsky (Editor)

In recent years, major developments have increased understanding of various genetic and epigenetic regulatory processes that are critical for the generation of B cell repertoires. These include the role of chromatin regulation and nuclear organization in understating the IgH gene regulation. These proceedings highlight recent developments in lymphocyte development, Ig gene rearrangements and somatic hypermutation, chromatin structure modification, B lymphocyte signaling and fate, receptor editing, and autoimmunity.

Antibodies that Cause Thyroid Diseases and Symptoms: Immune Cells causing Hypothyroidism & Hyperthyroidism
by James M. Lowrance (Author)

The majority of patients with both hypothyroidism (under-active thyroid) and hyperthyroidism (overactive thyroid) are experiencing autoimmune diseases that cause these conditions. When autoimmune thyroid disease results in hypothyroidism, the term for the disease is "Hashimoto's thyroiditis." When the autoimmune disease of the thyroid causes hyperthyroidism, it is called "Grave's Disease." Thyroid antibodies attack key proteins in the thyroid gland and in some cases, stimulate production of excessive amounts of hormone. These killer cells that are manufactured by the immune system become confused for reasons yet to be fully understood by medical science and they begin to identify thyroid cells as threats in the body. As they attack these cells, the thyroid gland becomes damaged, resulting...

Mathematical Models and Immune Cell Biology
by Carmen Molina-París (Editor), Grant Lythe (Editor)

Whole new areas of immunological research are emerging from the analysis of experimental data, going beyond statistics and parameter estimation into what an applied mathematician would recognise as modelling of dynamical systems. Stochastic methods are increasingly important, because stochastic models are closer to the Brownian reality of the cellular and sub-cellular world.

Molecular Mimicry in Health and Disease 1988: Interactions of Biological Substances with Neural, Endocrine and Immune Cells - Symposium Proceedings (International congress series)
by Ake Lernmark (Editor), etc. (Editor)

Transmembrane Potentials & Characters Immune & Tumor Cell
by Richard C. Niemtzow (Editor)

Clearance of Dying Cells in a Healthy and Diseased Immune System (Annals of the New York Academy of Sciences)
by Dror Mevorach (Editor)

The mode of death and the clearance of dying cells has a tremendous impact on immune tolerance and alters the clearance of dying cells, which may lead to autoimmunity and persistent inflammation. Inflammatory and "dangerous" modes of death influence the process of clearance and have a crucial role in cancer and interaction with organisms that may mimic molecules appearing dying cells. These observation lead to the need of an exchange emphasizing the mammalian immune system in the context of diseases, such as inflammatory and autoimmune diseases, cancer, and infections. This volume explores a number of topics in this area including mechanisms of tolerance induction by dying cells; mechanisms of danger induction by dying cells; infection and clearance of dying cells; autoimmunity,...

Cell Communication in Nervous and Immune System (Results and Problems in Cell Differentiation)
by Eckart D. Gundelfinger (Editor), Constanze Seidenbecher (Editor), Burkhart Schraven (Editor)

This collection of reviews contains contributions by internationally recognized immunologists and molecular and cellular neurobiologists. Uniquely, it puts side by side cellular communication devices and signaling mechanisms in the immune and nervous systems and discusses mechanisms of interaction between the two systems, the significance of which has only recently been fully appreciated.

Regulatory T Cells and Clinical Application
by Shuiping Jiang (Editor)

The immune system reacts vigorously to foreign invaders such as viruses, bacteria, protozoa, and parasites, and yet shows unresponsiveness to our own proteins. In the past decade, several types of T lymphocytes in the immune system have been discovered to function as regulatory cells to suppress unwanted immune responses to self-proteins, leading to the protection of autoimmunity. Furthermore, regulatory T cells also protect us from the development of asthma allergy, and prevent organ transplantation rejection. “Regulatory T Cells and Clinical Application” provides a comprehensive view of all types of regulatory T cells described so far in the literature. By thoroughly reviewing the immunobiology of regulatory T cells and their implications in various forms of human diseases, a new...