Projects per year
Abstract
T cells that produce both IL-17 and IFN-γ, and co-express ROR-γt and T-bet, are often found at sites of autoimmune inflammation. However, it is unknown whether this co-expression of T-bet with ROR-γt is a prerequisite for immunopathology. We show here that T-bet is not required for the development of Th17-driven experimental autoimmune encephalomyelitis (EAE). The disease was not impaired in T-bet−/− mice and was associated with low IFN-γ production and elevated IL-17 production among central nervous system (CNS) infiltrating CD4+ T cells. T-bet−/− Th17 cells generated in the presence of IL-6/TGF-β/IL-1 and IL-23 produced GM-CSF and high levels of IL-17 and induced disease upon transfer to naïve mice. Unlike their WT counterparts, these T-bet−/– Th17 cells did not exhibit an IL-17→IFN-γ switch upon reencounter with antigen in the CNS, indicating that this functional change is not critical to disease development. In contrast, T-bet was absolutely required for the pathogenicity of myelin-responsive Th1 cells. T-bet-deficient Th1 cells failed to accumulate in the CNS upon transfer, despite being able to produce GM-CSF. Therefore, T-bet is essential for establishing Th1-mediated inflammation but is not required to drive IL-23-induced GM-CSF production, or Th17-mediated autoimmune inflammation.
Original language | English |
---|---|
Pages (from-to) | 2818-2823 |
Number of pages | 6 |
Journal | European Journal of Immunology |
Volume | 43 |
Issue number | 11 |
DOIs | |
Publication status | Published - 1 Nov 2013 |
Fingerprint
Dive into the research topics of 'T-bet is essential for Th1-mediated, but not Th17-mediated, CNS autoimmune disease'. Together they form a unique fingerprint.Projects
- 3 Finished
-
-
The role of T-bet in Foxp3+ regulatory cell-mediated protection from autoimmune inflammation
Anderton, S. & O'Connor, R.
1/04/12 → 31/03/15
Project: Research
-
Immune cell interactions in the inflammed CNS
Anderton, S. & O'Connor, R.
1/04/09 → 30/09/14
Project: Research