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Fri May 18, 2012 8:34 am  |
Cytokines come in two basic varieties - inflammatory and anti-inflammatory. The inflammatory ones (associated with immune responses) have been the subject of research for many decades. And yeah, a big surge of the wrong ones can be deadly. In recent years we have discovered that this is held in check by the opposite - immune calming cytokines. They are all about growth and regeneration. And counteracting the immune stimulators.
This is what mesenchymal stem cells specialize in. They are so immune modulating that they are being exploited to treat all those things including autoimmune disease. They are our body's natural healers.
http://bloodjournal.hematologylibrary.org/content/105/4/1815.long
http://www.ncbi.nlm.nih.gov/pubmed/22515979
http://www.ncbi.nlm.nih.gov/pubmed/22586171
Curr Mol Med. 2012 Apr 18.
Immunosuppressive properties of mesenchymal stem cells: advances and applications.
Mesenchymal stem cells (MSCs) have been isolated from a variety of tissues, such as bone marrow, skeletal muscle, dental pulp, bone, umbilical cord and adipose tissue. MSCs are used in regenerative medicine mainly based on their capacity to differentiate into specific cell types and also as bioreactors of soluble factors that will promote tissue regeneration from the damaged tissue cellular progenitors. In addition to these regenerative properties, MSCs hold an immunoregulatory capacity, and elicit immunosuppressive effects in a number of situations. Not only are they immunoprivileged cells, due to the low expression of class II Major Histocompatibilty Complex (MHC-II) and costimulatory molecules in their cell surface, but they also interfere with different pathways of the immune response by means of direct cell-to-cell interactions and soluble factor secretion. In vitro, MSCs inhibit cell proliferation of T cells, B-cells, natural killer cells (NK) and dendritic cells (DC), producing what is known as division arrest anergy. Moreover, MSCs can stop a variety of immune cell functions: cytokine secretion and cytotoxicity of T and NK cells; B cell maturation and antibody secretion; DC maturation and activation; as well as antigen presentation. It is thought that MSCs need to be activated to exert their immunomodulation skills. In this scenario, an inflammatory environment seems to be necessary to promote their effect and some inflammation-related molecules such as tumor necrosis factor-α and interferon-γ might be implicated. It has been observed that MSCs recruit T-regulatory lymphocytes (Tregs) to both lymphoid organs and graft. There is great controversy concerning the mechanisms and molecules involved in the immunosuppressive effect of MSCs. Prostaglandin E2, transforming growth factor-β, interleukins- 6 and 10, human leukocyte antigen-G5, matrix metalloproteinases, indoleamine-2,3-dioxygenase and nitric oxide are all candidates under investigation. In vivo studies have shown many discrepancies regarding the immunomodulatory properties of MSCs. These studies have been designed to test the efficacy of MSC therapy in two different immune settings: the prevention or treatment of allograft rejection episodes, and the ability to suppress abnormal immune response in autoimmune and inflammatory diseases. Preclinical studies have been conducted in rodents, rabbits and baboon monkeys among others for bone marrow, skin, heart, and corneal transplantation, graft versus host disease, hepatic and renal failure, lung injury, multiple sclerosis, rheumatoid arthritis, diabetes and lupus diseases. Preliminary results from some of these studies have led to human clinical trials that are currently being carried out. These include treatment of autoimmune diseases such as Crohn's disease, ulcerative colitis, multiple sclerosis and type 1 diabetes mellitus; prevention of allograft rejection and enhancement of the survival of bone marrow and kidney grafts; and treatment of resistant graft versus host disease. We will try to shed light on all these studies, and analyze why the results are so contradictory.
They are also neuroprotective. Guard against all manner of toxicity.
http://www.ncbi.nlm.nih.gov/pubmed/22561409
This is a brand new finding I have discussed elsewhere:
Cell Stem Cell. 2012 May 4;10(5):485-7.
Autoimmune T Cells Lured to a FASL Web of Death by MSCs.
Murphy WJ, Nolta JA.
Source
Department of Dermatology, University of California, Davis, Davis, CA 95616, USA; Department of Internal Medicine, University of California, Davis, Davis, CA 95616, USA.
Abstract
Achieving immune tolerance through cell transplantation is a promising approach for treating autoimmune disease. In this issue of Cell Stem Cell, Akiyama et al. (2012) demonstrate that human and mouse mesenchymal stem cells can induce immune suppression by attracting and killing autoreactive T cells, which stimulates TGFb production by macrophages and generates regulatory T cells.
The future of autoimmune disease, and all those other "cytokine mediated" things, is cytokines. The right ones, from just the right cells. |
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Sat May 19, 2012 11:08 pm |
Fascinating stuff.
So we all have normally healing cytokines, but sometimes they need a boost of healthy cytokines? Or in diseases those cytokines give a sick message from cell to cell to cell?
You say, "the right ones from just the right cells". Cytokines, apparently, are specific in their mission? |
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| Thu Nov 21, 2024 3:39 am |
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