So after reading the McInness article on Cytokines in the pathogenesis of rheumatoid arthritis I was left with the feeling Th17 cells equal a bad situation for autoimmune disease. Which typically seems to be the case in most if not all disease states, and is been looked at as a target in several diseases states from RA to MS. However, I have been doing some outside reading on type 1 diabetes (T1D), another autoimmune disease where Th17 is implicated. However, it seems that it may actually have a protective effect in NOD mice (non obese diabetes mice), one of the two typical mouse models used in studying T1D. The theory is that Th1 cells are primarily responsible for beta-cell apoptosis; thus if we can sustain Th17 cells rather than increasing proliferation of Th1 cells we see less incidence of T1D in these mice. So the authors in several papers associate at IL-6 and IL-12 as positive outcomes as these cytokines promote and sustain Th17 cells. This is obviously a new thought and slightly controversial; but brings to mind how much we really don't know about all the factors involved in different inflammatory pathways. And in blocking or diminishing a one cell type cell in a autoimmune condition my actually be detrimental in another. Food for thought....
Han et al. Interleukin-17 producing gamma+ T cells protect NOD mice from type 1 diabetes through a mechanism involving transforming growth factor-beta. Immunology. 2009;197-206
Nikoopour et al. Th17 Polarized cells from NOD mice following mycobacterial adjuvant immunotherapy delay type 1 diabetes. The Journal of Immnology. 2010;4779-88.
I was also interested with the effects of Th17 cells on certain autoimmune diseases and it seems that they play an important role in regulating autoimmune diseases by releasing cytokines that regulate other T cells. Because they are so new to our knowledge I believe there is still a lot more research to be done on the effects of Th17 cells, although many believe that they are vital for regulation of the immune system. IL-17 is released from these specific cells and supposedly activates stromal cells to secrete IL-6 and IL-8, both pro-inflammatory cytokines. It seems as if these cells help promote a localized response in the body by activating specific stromal cells close to the tissue that is being effected. Unfortunately we see the action of Th17 cells promoting overly inflammatory responses such as in rheumatoid arthritis and in Crohn's disease. The next step is to more fully understand these cells and find out why they create an excessive autoimmune response.
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ReplyDeleteVery good information about Th17 cells. These cells have been identified as a unique subset of T-helper cells and constitute a subset of cells known as neutrophil regulatory T-cells....
Apoptosis Detection