title: Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis.
abstract: Naive T helper cells differentiate into functionally distinct effector subsets that drive specialized immune responses. Recent studies indicate that some of the effector subsets have plasticity. Here, we used an EAE model and found that Th17 cells deficient in the transcription factor BCL11B upregulated the Th2-associated proteins GATA3 and IL-4 without decreasing RAR-related orphan receptor γ (RORγt), IL-17, and GM-CSF levels. Surprisingly, abnormal IL-4 production affected Th17 cell trafficking, diverting migration from the draining lymph nodes/CNS route to the mesenteric lymph nodes/gut route, which ameliorated EAE without overt colitis. T helper cell rerouting in EAE was dependent on IL-4, which enhanced retinoic acid (RA) production by dendritic cells, which further induced expression of gut-homing receptors CCR9 and α4β7 on Bcl11b-deficient CD4+ T cells. Furthermore, IL-4 treatment or Th2 immunization of wild-type mice with EAE caused no alteration in Th17 cytokines or RORγt, but diverted T helper cell trafficking to the gut, which improved EAE outcome without overt colitis. Our data demonstrate that Th17 cells are permissive to Th2 gene expression without affecting Th17 gene expression. This Th17 plasticity has an impact on trafficking, which is a critical component of the immune response and may represent a possible avenue for treating multiple sclerosis.
authors: Danielle
authors: D
authors: Califano
authors: Keith J
authors: KJ
authors: Sweeney
authors: Hung
authors: H
authors: Le
authors: Jeffrey
authors: J
authors: VanValkenburgh
authors: Eric
authors: E
authors: Yager
authors: William
authors: W
authors: O'Connor
authors: Jeffrey S
authors: JS
authors: Kennedy
authors: David M
authors: DM
authors: Jones
authors: Dorina
authors: D
authors: Avram
mesh_terms: D000818:Animals; D002465:Cell Movement; D016764:Cell Polarity; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D005260:Female; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D007167:Immunotherapy; D020381:Interleukin-17 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D012097:Repressor Proteins / Q000502:physiology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology*; D014212:Tretinoin / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: C511143:Bcl11b protein, mouse; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; D015847:Interleukin-4; D014212:Tretinoin; D016178:Granulocyte-Macrophage Colony-Stimulating Factor