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- Title
Diverting T helper cell trafficking through increased plasticity attenuates autoimmune encephalomyelitis.
- Authors
Califano, Danielle; Sweeney, Keith J.; Hung Le; VanValkenburgh, Jeffrey; Yager, Eric; O'Connor, William; Kennedy, Jeffrey S.; Jones, David M.; Avram, Dorina
- 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 Thl7 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 Thl7 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 Bell lb-deficient CD4+ T cells. Furthermore, IL-4 treatment or Th2 immunization of wild-type mice with EAE caused no alteration in Th17 cytokines or RORyγt, 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 Thl7 gene expression. This Thl7 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.
- Subjects
T helper cells; CELLULAR immunity; TRANSCRIPTION factors; DENDRITIC cells; PHENOTYPIC plasticity
- Publication
Journal of Clinical Investigation, 2014, Vol 124, Issue 1, p174
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI70103