HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

FoxP3+RORgammat+ T helper intermediates display suppressive function against autoimmune diabetes.

Abstract
Recently, traces of double-positive FoxP3(+)RORgammat(+) T cells were identified and viewed as dual programming differentiation intermediates geared toward development into T regulatory or Th17 cells. In this study, we report that FoxP3(+)RORgammat(+) intermediates arise in the NOD mouse T cell repertoire prior to inflammation and can be expanded with tolerogen without further differentiation. Furthermore, FoxP3(+)RORgammat(+) cells express both CD62L and membrane-bound TGFbeta and use the former to traffic to the pancreas and the latter to suppress effector T cells both in vitro and in vivo. The cells perform these functions as FoxP3(+)RORgammat(+) intermediates, despite being able to terminally differentiate into either FoxP3(+)RORgammat(-) T regulatory or FoxP3(-)RORgammat(+) Th17 cells on polarization. These previously unrecognized observations extend plasticity to both differentiation and function and indicate that the intermediates are poised to traffic to sites of inflammation and target diverse pathogenic T cells, likely without prior conditioning by effector T cells, thus broadening efficacy against autoimmunity.
AuthorsDanielle M Tartar, Amie M VanMorlan, Xiaoxiao Wan, F Betul Guloglu, Renu Jain, Cara L Haymaker, Jason S Ellis, Christine M Hoeman, Jason A Cascio, Mermagya Dhakal, Mohamed Oukka, Habib Zaghouani
JournalJournal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 7 Pg. 3377-85 (Apr 01 2010) ISSN: 1550-6606 [Electronic] United States
PMID20181889 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-17
  • Nuclear Receptor Subfamily 1, Group F, Member 3
Topics
  • Animals
  • Cell Differentiation (immunology)
  • Cell Separation
  • Diabetes Mellitus, Type 1 (immunology, metabolism)
  • Flow Cytometry
  • Forkhead Transcription Factors (immunology, metabolism)
  • Interleukin-17 (immunology, metabolism)
  • Lymphocyte Activation (immunology)
  • Mice
  • Mice, Inbred NOD
  • Nuclear Receptor Subfamily 1, Group F, Member 3 (immunology, metabolism)
  • Reverse Transcriptase Polymerase Chain Reaction
  • T-Lymphocyte Subsets (cytology, immunology, metabolism)
  • T-Lymphocytes, Helper-Inducer (cytology, immunology, metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: