The protein tyrosine kinase Tec regulates a CD44highCD62L- Th17 subset.
The generation of Th17 cells has to be tightly controlled during an immune response. In this study, we report an increase in a CD44(high)CD62L(-) Th17 subset in mice deficient for the protein tyrosine kinase Tec. CD44(high)CD62L(-) Tec(-/-) CD4(+) T cells produced enhanced IL-17 upon activation, showed increased expression levels of IL-23R and RORγt, and IL-23-mediated expansion of Tec(-/-) CD4(+) T cells led to an increased production of IL-17. Tec(-/-) mice immunized with heat-killed Streptococcus pneumoniae displayed increased IL-17 expression levels in the lung postinfection with S. pneumoniae, and this correlated with enhanced pneumococcal clearance and reduced lung inflammation compared with Tec(+/+) mice. Moreover, naive Tec(-/-) OT-II CD4(+) T cells produced higher levels of IL-17 when cultured with OVA peptide-loaded bone marrow-derived dendritic cells that have been previously activated with heat-killed S. pneumoniae. Taken together, our data indicated a critical role for Tec in T cell-intrinsic signaling pathways that regulate the in vivo generation of CD44(high)CD62L(-) effector/memory Th17 populations.
Boucheron
Nicole
N
Division of Immunobiology, Institute of Immunology, Medical University of Vienna, Vienna, Austria.
Sharif
Omar
O
Schebesta
Alexandra
A
Croxford
Andrew
A
Raberger
Julia
J
Schmidt
Uwe
U
Vigl
Benjamin
B
Bauer
Jan
J
Bankoti
Rashmi
R
Lassmann
Hans
H
Epstein
Michelle M
MM
Knapp
Sylvia
S
Waisman
Ari
A
Ellmeier
Wilfried
W
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage; D002469:Cell Separation; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018960:Hyaluronan Receptors / Q000276:immunology / Q000378:metabolism; D015151:Immunoblotting; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D019041:L-Selectin / Q000276:immunology / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011014:Pneumonia / Q000276:immunology; D011505:Protein-Tyrosine Kinases / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000201:enzymology / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000201:enzymology / Q000276:immunology*
D016207:Cytokines; D018960:Hyaluronan Receptors; D020381:Interleukin-17; D019041:L-Selectin; C089848:Tec protein-tyrosine kinase; D011505:Protein-Tyrosine Kinases