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CD69 association with Jak3/Stat5 proteins regulates Th17 cell differentiation
- Source :
- Molecular and cellular biology. 30(20)
- Publication Year :
- 2010
-
Abstract
- T-cell differentiation involves the early decision to commit to a particular pattern of response to an antigen. Here, we show that the leukocyte activation antigen CD69 limits differentiation into proinflammatory helper T cells (Th17 cells). Upon antigen stimulation in vitro, CD4(+) T cells from CD69-deficient mice generate an expansion of Th17 cells and the induction of greater mRNA expression of interleukin 17 (IL-17), IL 23 receptor (IL-23R), and the nuclear receptor retinoic acid-related orphan receptor γt (RORγt). In vivo studies with CD69-deficient mice bearing OTII T-cell receptors (TCRs) specific for OVA peptide showed a high proportion of antigen-specific Th17 subpopulation in the draining lymph nodes, as well as in CD69-deficient mice immunized with type II collagen. Biochemical analysis demonstrated that the CD69 cytoplasmic tail associates with the Jak3/Stat5 signaling pathway, which regulates the transcription of RORγt and, consequently, differentiation toward the Th17 lineage. Functional experiments in Th17 cultures demonstrated that the selective inhibition of Jak3 activation enhanced the transcription of RORγt. Moreover, the addition of exogenous IL-2 restored Stat5 phosphorylation and inhibited the enhanced Th17 differentiation in CD69-deficient cells. These results support the early activation receptor CD69 as an intrinsic modulator of the T-cell differentiation program that conditions immune inflammatory processes.
- Subjects :
- Antigens, Differentiation, T-Lymphocyte
CD4-Positive T-Lymphocytes
Male
Ovalbumin
Cellular differentiation
Molecular Sequence Data
chemical and pharmacologic phenomena
Mice, Transgenic
Biology
In Vitro Techniques
Lymphocyte Activation
Mice
Immune system
Antigen
RAR-related orphan receptor gamma
Antigens, CD
STAT5 Transcription Factor
Animals
Lectins, C-Type
Amino Acid Sequence
RNA, Messenger
Receptor
Molecular Biology
DNA Primers
Orphan receptor
Mice, Knockout
Mice, Inbred BALB C
Base Sequence
Interleukin-17
Janus Kinase 3
hemic and immune systems
Cell Differentiation
Cell Biology
Receptors, Interleukin
T-Lymphocytes, Helper-Inducer
Articles
Nuclear Receptor Subfamily 1, Group F, Member 3
Molecular biology
Mice, Inbred C57BL
Nuclear receptor
Multiprotein Complexes
Interleukin-2
Female
Signal transduction
Signal Transduction
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 30
- Issue :
- 20
- Database :
- OpenAIRE
- Journal :
- Molecular and cellular biology
- Accession number :
- edsair.doi.dedup.....3aa4de7f35bc7a19e92c96e31783bb1e