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Article: The NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells

TitleThe NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells
Authors
Issue Date2012
Citation
Journal of Clinical Investigation, 2012, v. 122, n. 12, p. 4698-4709 How to Cite?
AbstractEffector functions of inflammatory IL-17-producing Th (Th17) cells have been linked to autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). However, what determines Th17 cell encephalitogenicity is still unresolved. Here, we show that after EAE induction, mice deficient for the NF-κB regulator MALT1 (Malt1-/- mice) exhibit strong lymphocytic infiltration in the CNS, but do not develop any clinical signs of EAE. Loss of Malt1 interfered with expression of the Th17 effector cytokines IL-17 and GM-CSF both in vitro and in vivo. In line with their impaired GM-CSF secretion, Malt1-/- Th cells failed to recruit myeloid cells to the CNS to sustain neuroinflammation, whereas autoreactive WT Th cells successfully induced EAE in Malt1-/- hosts. In contrast, Malt1 deficiency did not affect Th1 cells. Despite their significantly decreased secretion of Th17 effector cytokines, Malt1 -/- Th17 cells showed normal expression of lineage-specific transcription factors. Malt1-/- Th cells failed to cleave RelB, a suppressor of canonical NF-κB, and exhibited altered cellular localization of this protein. Our results indicate that MALT1 is a central, cell-intrinsic factor that determines the encephalitogenic potential of inflammatory Th17 cells in vivo.
Persistent Identifierhttp://hdl.handle.net/10722/292026
ISSN
2023 Impact Factor: 13.3
2023 SCImago Journal Rankings: 4.833
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorBrüstle, Anne-
dc.contributor.authorBrenner, Dirk-
dc.contributor.authorKnobbe, Christiane B.-
dc.contributor.authorLang, Philipp A.-
dc.contributor.authorVirtanen, Carl-
dc.contributor.authorHershenfield, Brian M.-
dc.contributor.authorReardon, Colin-
dc.contributor.authorLacher, Sonja M.-
dc.contributor.authorRuland, Jürgen-
dc.contributor.authorOhashi, Pamela S.-
dc.contributor.authorMak, Tak W.-
dc.date.accessioned2020-11-17T14:55:37Z-
dc.date.available2020-11-17T14:55:37Z-
dc.date.issued2012-
dc.identifier.citationJournal of Clinical Investigation, 2012, v. 122, n. 12, p. 4698-4709-
dc.identifier.issn0021-9738-
dc.identifier.urihttp://hdl.handle.net/10722/292026-
dc.description.abstractEffector functions of inflammatory IL-17-producing Th (Th17) cells have been linked to autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS). However, what determines Th17 cell encephalitogenicity is still unresolved. Here, we show that after EAE induction, mice deficient for the NF-κB regulator MALT1 (Malt1-/- mice) exhibit strong lymphocytic infiltration in the CNS, but do not develop any clinical signs of EAE. Loss of Malt1 interfered with expression of the Th17 effector cytokines IL-17 and GM-CSF both in vitro and in vivo. In line with their impaired GM-CSF secretion, Malt1-/- Th cells failed to recruit myeloid cells to the CNS to sustain neuroinflammation, whereas autoreactive WT Th cells successfully induced EAE in Malt1-/- hosts. In contrast, Malt1 deficiency did not affect Th1 cells. Despite their significantly decreased secretion of Th17 effector cytokines, Malt1 -/- Th17 cells showed normal expression of lineage-specific transcription factors. Malt1-/- Th cells failed to cleave RelB, a suppressor of canonical NF-κB, and exhibited altered cellular localization of this protein. Our results indicate that MALT1 is a central, cell-intrinsic factor that determines the encephalitogenic potential of inflammatory Th17 cells in vivo.-
dc.languageeng-
dc.relation.ispartofJournal of Clinical Investigation-
dc.titleThe NF-κB regulator MALT1 determines the encephalitogenic potential of Th17 cells-
dc.typeArticle-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1172/JCI63528-
dc.identifier.pmid23114599-
dc.identifier.pmcidPMC3590210-
dc.identifier.scopuseid_2-s2.0-84870521827-
dc.identifier.volume122-
dc.identifier.issue12-
dc.identifier.spage4698-
dc.identifier.epage4709-
dc.identifier.eissn1558-8238-
dc.identifier.isiWOS:000311926200042-
dc.identifier.issnl0021-9738-

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