Integration of Th17- and Lymphotoxin-Derived Signals Initiates Meningeal-Resident Stromal Cell Remodeling to Propagate Neuroinflammation
| Autor: | Hanane Touil, Brendan Heiden, Samuel K. Ludwin, Paul O'Connor, Jennifer L. Gommerman, Valera Castanov, Deepali Malhotra, Robert Kay, Shannon J. Turley, Alexandre Prat, Natalia Pikor, Amit Bar-Or, Lesley A. Ward, Joy Qu, Susan J. Armstrong, Georgina Galicia, Jillian L. Astarita, Valeria Ramaglia, Louis Boon, Leslie Summers-Deluca, Claudia X. Dominguez |
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| Rok vydání: | 2015 |
| Předmět: |
Adult
CD4-Positive T-Lymphocytes Male Lymphotoxin alpha Chemokine Encephalomyelitis Autoimmune Experimental Stromal cell Immunology Inflammation Polymerase Chain Reaction Extracellular matrix Mice 03 medical and health sciences Meninges Multiple Sclerosis Relapsing-Remitting 0302 clinical medicine medicine Animals Humans Immunology and Allergy Lymphotoxin-alpha Neuroinflammation 030304 developmental biology Mice Knockout 0303 health sciences biology Flow Cytometry Immunohistochemistry Cell biology Infectious Diseases medicine.anatomical_structure Lymphotoxin biology.protein Th17 Cells Female Stromal Cells medicine.symptom Signal Transduction 030215 immunology |
| Zdroj: | Immunity. 43:1160-1173 |
| ISSN: | 1074-7613 |
| Popis: | SummaryTertiary lymphoid tissues (TLTs) have been observed in the meninges of multiple sclerosis (MS) patients, but the stromal cells and molecular signals that support TLTs remain unclear. Here, we show that T helper 17 (Th17) cells induced robust TLTs within the brain meninges that were associated with local demyelination during experimental autoimmune encephalitis (EAE). Th17-cell-induced TLTs were underpinned by a network of stromal cells producing extracellular matrix proteins and chemokines, enabling leukocytes to reside within, rather than simply transit through, the meninges. Within the CNS, interactions between lymphotoxin αβ (LTαβ) on Th17 cells and LTβR on meningeal radio-resistant cells were necessary for the propagation of de novo interleukin-17 responses, and activated T cells from MS patients expressed elevated levels of LTβR ligands. Therefore, input from both Th17 cells and the lymphotoxin pathway induce the formation of an immune-competent stromal cell niche in the meninges. |
| Databáze: | OpenAIRE |
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