Article

Furuzawa-Carballeda J, Vargas-Rojas MI, Cabral ARAutoimmune inflammation from the Th17 perspective. Autoimmun Rev 6:169-175

Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Vasco de Quiroga 15 Tlalpan, Mexico City 14000, Mexico.
Autoimmunity Reviews (Impact Factor: 7.93). 02/2007; 6(3):169-75. DOI: 10.1016/j.autrev.2006.10.002
Source: PubMed

ABSTRACT

Recent studies demonstrated an IL-17-producer CD4+ T cell subpopulation, termed Th17, distinct from Th1 and Th2. It represents a different pro-inflammatory Th-cell lineage. This notion is supported by gene-targeted mice studies. Mice lacking IL-23 (p19-/-) do not develop experimental autoimmune encephalomyelitis (EAE) or collagen-induced arthritis (CIA), while knockout mice for the Th1 cytokine IL-12 (p35-/-) strongly develop both autoimmune diseases. Disease resistance by IL-23 knockout mice correlates well with the absence of IL-17-producing CD4(+) T lymphocytes in target organs despite normal presence of antigen-specific-IFN-gamma-producing Th1 cells. This finding may thus explain previous contradictory reports showing that anti-IFN-gamma-treated mice, IFN-gamma- or IFNR-deficient mice develop CIA or EAE. TGF-beta, IL-6 and IL-1 are the differentiation factors of Th17 cells. IL-23 is dispensable for this function, but necessary for Th17 expansion and survival. The master regulator that directs the differentiation program of Th17 cells is the orphan nuclear receptor RORgammat. IL-27, a member of the IL-12/IL-23 family, potently inhibits Th17 development. Evidence suggesting rheumatoid arthritis and multiple sclerosis as primarily IL-17 autoimmune inflammatory-mediated diseases is rapidly accumulating. The IL-17/23 axis of inflammation and related molecules may rise as therapeutic targets for treating these and perhaps other autoimmune diseases.

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Available from: Janette Furuzawa-Carballeda
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    • "However, the results in the amphibole mice clearly suggest a TH17 response. The TH17 response is characterized by high levels of IL-17, triggered or maintained by other cytokines such as IL-6, IL-23, and TGF-beta [73]. TH17 responses have been implicated in a variety of diseases, including RA, SSc, and SLE [74–76]. "
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    • "To date, however, there have only been a few trials of antibiotic prophylaxis following a stroke and these relatively small trials have conflicting results, suggesting that prophylactic antibiotic therapy may improve, worsen, or have no effect on the stroke outcome (Schwartz S 2008, Chomorro A 2005, Harms H 2008). IL-17 was recently shown to contribute to ischemic brain injury up to 7 days after the onset of a stroke (Schichita T 2009) In this study, the IL-17 was being produced by Ȗδ T cells, which are important mediators in the antigen non-specific inflammatory response, and not by TH17 cells. Given the fact that there is robust upregulation of IL-6 following a stroke and increased expression of TGF-ȕ1 in brain, however, the post-ischemic cytokine milieu could favor the development of TH17 cells (Krupinski J 1996, Wang X 1995) Whether or not CNS specific TH17 cells contribute to injury in cerebral ischemia has yet to be explored, but their importance in autoimmune diseases, including experimental allergic encephalomyelitis (EAE), is clear (Furuzawa-Carballeda J 2007, Hoffstetter H 2009). Recent data highlight the fact that the ratio of antigen specific TH17 cells to antigen specific TH1 cells as well as the cell type used to induce EAE (TH17 versus TH1) influence both EAE phenotype and pathology (Jager A 2009, Stromnes IM 2008). These data further suggest that the nature of the immune response to brain after a stroke has the potential to differentially affect outcome. "
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    • "To date, however, there have only been a few trials of antibiotic prophylaxis following a stroke and these relatively small trials have conflicting results, suggesting that prophylactic antibiotic therapy may improve, worsen, or have no effect on the stroke outcome (Schwartz S 2008, Chomorro A 2005, Harms H 2008). IL-17 was recently shown to contribute to ischemic brain injury up to 7 days after the onset of a stroke (Schichita T 2009) In this study, the IL-17 was being produced by Ȗδ T cells, which are important mediators in the antigen non-specific inflammatory response, and not by TH17 cells. Given the fact that there is robust upregulation of IL-6 following a stroke and increased expression of TGF-ȕ1 in brain, however, the post-ischemic cytokine milieu could favor the development of TH17 cells (Krupinski J 1996, Wang X 1995) Whether or not CNS specific TH17 cells contribute to injury in cerebral ischemia has yet to be explored, but their importance in autoimmune diseases, including experimental allergic encephalomyelitis (EAE), is clear (Furuzawa-Carballeda J 2007, Hoffstetter H 2009). Recent data highlight the fact that the ratio of antigen specific TH17 cells to antigen specific TH1 cells as well as the cell type used to induce EAE (TH17 versus TH1) influence both EAE phenotype and pathology (Jager A 2009, Stromnes IM 2008). These data further suggest that the nature of the immune response to brain after a stroke has the potential to differentially affect outcome. "
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