Differential regulation of central nervous system autoimmunity by TH1 and TH17 cells
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TLDR
It is demonstrated that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (TH17) to T helpertype 1 (TH1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes.Abstract:
Multiple sclerosis is an inflammatory, demyelinating disease of the central nervous system (CNS) characterized by a wide range of clinical signs1 The location of lesions in the CNS is variable and is a crucial determinant of clinical outcome Multiple sclerosis is believed to be mediated by myelin-specific T cells, but the mechanisms that determine where T cells initiate inflammation are unknown Differences in lesion distribution have been linked to the HLA complex, suggesting that T cell specificity influences sites of inflammation2 We demonstrate that T cells that are specific for different myelin epitopes generate populations characterized by different T helper type 17 (TH17) to T helper type 1 (TH1) ratios depending on the functional avidity of interactions between TCR and peptide-MHC complexes Notably, the TH17:TH1 ratio of infiltrating T cells determines where inflammation occurs in the CNS Myelin-specific T cells infiltrate the meninges throughout the CNS, regardless of the TH17:TH1 ratio However, T cell infiltration and inflammation in the brain parenchyma occurs only when TH17 cells outnumber TH1 cells and trigger a disproportionate increase in interleukin-17 expression in the brain In contrast, T cells showing a wide range of TH17:TH1 ratios induce spinal cord parenchymal inflammation These findings reveal critical differences in the regulation of inflammation in the brain and spinal cordread more
Citations
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Regulatory T Cells: Mechanisms of Differentiation and Function
TL;DR: Cellular and molecular mechanisms in the differentiation and function of regulatory T cells and their role in autoimmune and autoinflammatory disorders, allergy, acute and chronic infections, cancer, and metabolic inflammation are discussed.
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C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE
Andrea Reboldi,Caroline Coisne,Dirk Baumjohann,Federica Benvenuto,Denise Bottinelli,Sergio A. Lira,Antonio Uccelli,Antonio Lanzavecchia,Britta Engelhardt,Federica Sallusto +9 more
TL;DR: These results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS.
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Fate mapping of IL-17-producing T cells in inflammatory responses
Keiji Hirota,João H. Duarte,Marc Veldhoen,Marc Veldhoen,Eve Hornsby,Ying Li,Daniel J. Cua,Helena Ahlfors,Christoph Wilhelm,Mauro Tolaini,Ursula Menzel,Anna Garefalaki,Alexandre J. Potocnik,Brigitta Stockinger +13 more
TL;DR: A reporter mouse strain designed to map the fate of cells that have activated interleukin 17A (IL-17A) allows the actual functional fate of effector T cells to be related to TH17 developmental origin regardless of IL-17 expression.
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Autoimmune T cell responses in the central nervous system
TL;DR: This Review focuses on recent progress in delineating the pathogenic mechanisms, regulation and interplay between these different T cell subsets in CNS autoimmunity.
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T cells in multiple sclerosis and experimental autoimmune encephalomyelitis
TL;DR: The contribution of Th1, Th17, γδ, CD8+ and regulatory T cells as well as the possible development of new therapeutic approaches for MS based on manipulating these T cell subtypes are reviewed.
References
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Journal ArticleDOI
Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Laurie E. Harrington,Robin D. Hatton,Paul R. Mangan,Henrietta Turner,Theresa L. Murphy,Kenneth M. Murphy,Casey T. Weaver +6 more
TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Journal ArticleDOI
Immunology of multiple sclerosis
Mireia Sospedra,Roland Martin +1 more
TL;DR: In the early stages of MS, the activation of CD4+ autoreactive T cells and their differentiation into a Th1 phenotype are a crucial events in the initial steps, and these cells are probably also important players in the long-term evolution of the disease.
Journal ArticleDOI
A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage.
TL;DR: The evolution of the understanding of the TH17 pathway illuminates a shift in immunologists' perspectives regarding the basis of tissue damage, where for over 20 years the role of TH1 cells was considered paramount.
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Metalloproteinases in biology and pathology of the nervous system
TL;DR: Some of the beneficial functions of MMPs during neural development are considered and their roles in repair after brain injury are speculated, as well as a family of proteins known as ADAMs, as some of the properties previously ascribed to M MPs are possibly the result of ADAM activity.