FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W4235395943> ?p ?o ?g. }

• W4235395943 endingPage "S83" @default.
• W4235395943 startingPage "S83" @default.
• W4235395943 abstract "Gastrointestinal (GI) tract represents an important interphase between the body and the outside world. Under steady-state conditions, T-cellassociated α4 integrins (α4β7, α4β1) play an important role in T-cell recruitment to the gut-associated lymphoid tissue (GALT: Peyer's Patches, lymphoid follicles), mesenteric lymph nodes (MLNs) and small intestine. Moreover, these molecules are important contributors to the pathogenesis of experimental and human Crohn's disease (CD). Although the effectiveness of anti-adhesion therapy targeting α4 integrins is thought to be primarily due to blocking effector T cell recruitment into intestinal tissues, there is little direct evidence to confirm this, since α4 integrins can be also found on natural killer cells, monocytes, and granulocytes. Therefore, the objective of the current study was to ascertain the importance of T cell-associated α4 integrins in the induction of chronic gut inflammation. We utilized cre/loxP technology to generate conditional mutant mice with T cells lacking α4 integrins (α4-/-). Using adoptive T cell transfer model of CD, we reconstituted recombination activating gene-deficient (RAG-1-/-) mice with α4-/- or control α4+/+ CD4+CD45RBhigh T cells and monitored development of disease. Blinded histopathological colon scores, infiltrating leukocyte numbers and phenotype, and cytokine production by colon lamina propria (LP) cells were determined. To determine the effect of α4 integrin deletion on T cell trafficking, we conducted competitive homing experiments. While α4+/+ T cells elicited moderate to severe colitis, colitis in the α4-/-→RAG-1-/- mice was remarkably attenuated. This correlated with a significant reduction in T cells, granulocytes, and monocytes in colons of these mice compared to the α4+/+→RAG-1-/- group. Analysis of cytokines produced by mononuclear cells isolated from colon LP in the α4-/-→RAG-1-/- mice showed reduced levels of IL-1β, IL-2, IL-17, and TNF-α but not IFN-γ or IL-12p70 compared to control. Single-cell analysis of CD4+ T cells by intracellular staining revealed comparable production of IFN-γ and IL-17 by α4-/- and α4+/+, suggesting that α4-/- T cells are not defective in their ability to become activated and secrete pro-inflammatory cytokines. Trafficking of α4-/- and control T cells to MLN was comparable to WT, while homing of α4-/- T cells to small intestine and colon was severely compromised. Finally, analysis of surface integrins in reconstituted mice revealed that following transmigration into colon LP, T cells downregulate α4β7 but maintain high levels of β1 integrin expression. Alpha4 integrins are important for intravascular recruitment of T cells to the intestine and induction of colitis. At the same time, our data suggested that β1 integrins may be important for their localization within the intestinal tissue. Further work will need to determine relative importance of these integrins in the ability of T cells to induce experimental colitis." @default.
• W4235395943 created "2022-05-12" @default.
• W4235395943 creator A5003027894 @default.
• W4235395943 creator A5032752812 @default.
• W4235395943 creator A5044314141 @default.
• W4235395943 creator A5066378622 @default.
• W4235395943 creator A5079788124 @default.
• W4235395943 date "2012-12-01" @default.
• W4235395943 modified "2023-09-26" @default.
• W4235395943 title "Mechanisms of Protection of Alpha4-Deficient T Cells in a Model of Chronic Experimental Colitis" @default.
• W4235395943 doi "https://doi.org/10.1097/00054725-201212001-00204" @default.
• W4235395943 hasPublicationYear "2012" @default.
• W4235395943 type Work @default.
• W4235395943 citedByCount "0" @default.
• W4235395943 crossrefType "journal-article" @default.
• W4235395943 hasAuthorship W4235395943A5003027894 @default.
• W4235395943 hasAuthorship W4235395943A5032752812 @default.
• W4235395943 hasAuthorship W4235395943A5044314141 @default.
• W4235395943 hasAuthorship W4235395943A5066378622 @default.
• W4235395943 hasAuthorship W4235395943A5079788124 @default.
• W4235395943 hasBestOaLocation W42353959431 @default.
• W4235395943 hasConcept C142724271 @default.
• W4235395943 hasConcept C1491633281 @default.
• W4235395943 hasConcept C151872237 @default.
• W4235395943 hasConcept C154317977 @default.
• W4235395943 hasConcept C18903297 @default.
• W4235395943 hasConcept C195687474 @default.
• W4235395943 hasConcept C202751555 @default.
• W4235395943 hasConcept C203014093 @default.
• W4235395943 hasConcept C2775862500 @default.
• W4235395943 hasConcept C2776090121 @default.
• W4235395943 hasConcept C2777310793 @default.
• W4235395943 hasConcept C4175445 @default.
• W4235395943 hasConcept C529295009 @default.
• W4235395943 hasConcept C54355233 @default.
• W4235395943 hasConcept C55493867 @default.
• W4235395943 hasConcept C71924100 @default.
• W4235395943 hasConcept C86803240 @default.
• W4235395943 hasConcept C8891405 @default.
• W4235395943 hasConcept C90375314 @default.
• W4235395943 hasConceptScore W4235395943C142724271 @default.
• W4235395943 hasConceptScore W4235395943C1491633281 @default.
• W4235395943 hasConceptScore W4235395943C151872237 @default.
• W4235395943 hasConceptScore W4235395943C154317977 @default.
• W4235395943 hasConceptScore W4235395943C18903297 @default.
• W4235395943 hasConceptScore W4235395943C195687474 @default.
• W4235395943 hasConceptScore W4235395943C202751555 @default.
• W4235395943 hasConceptScore W4235395943C203014093 @default.
• W4235395943 hasConceptScore W4235395943C2775862500 @default.
• W4235395943 hasConceptScore W4235395943C2776090121 @default.
• W4235395943 hasConceptScore W4235395943C2777310793 @default.
• W4235395943 hasConceptScore W4235395943C4175445 @default.
• W4235395943 hasConceptScore W4235395943C529295009 @default.
• W4235395943 hasConceptScore W4235395943C54355233 @default.
• W4235395943 hasConceptScore W4235395943C55493867 @default.
• W4235395943 hasConceptScore W4235395943C71924100 @default.
• W4235395943 hasConceptScore W4235395943C86803240 @default.
• W4235395943 hasConceptScore W4235395943C8891405 @default.
• W4235395943 hasConceptScore W4235395943C90375314 @default.
• W4235395943 hasLocation W42353959431 @default.
• W4235395943 hasOpenAccess W4235395943 @default.
• W4235395943 hasPrimaryLocation W42353959431 @default.
• W4235395943 hasRelatedWork W1997140307 @default.
• W4235395943 hasRelatedWork W2034661186 @default.
• W4235395943 hasRelatedWork W2096515408 @default.
• W4235395943 hasRelatedWork W2102067914 @default.
• W4235395943 hasRelatedWork W2152945646 @default.
• W4235395943 hasRelatedWork W2171853585 @default.
• W4235395943 hasRelatedWork W2269980737 @default.
• W4235395943 hasRelatedWork W2320945754 @default.
• W4235395943 hasRelatedWork W2334181930 @default.
• W4235395943 hasRelatedWork W3193315220 @default.
• W4235395943 hasVolume "18" @default.
• W4235395943 isParatext "false" @default.
• W4235395943 isRetracted "false" @default.
• W4235395943 workType "article" @default.