c-Rel is crucial for the induction of Foxp3(+) regulatory CD4(+) T cells but not T(H)17 cells.
The NF-kappaB/Rel family member c-Rel was described to be required for the development of T(H)1 responses. However, the role of c-Rel in the differentiation of T(H)17 and regulatory CD4(+)Foxp3(+) T cells (Treg) remains obscure. Here, we show that in the absence of c-Rel, in vitro differentiation of pro-inflammatory T(H)17 cells is normal. In contrast, generation of inducible Treg (iTreg) within c-Rel-deficient CD4(+) T cells was severely hampered and correlated to reduced numbers of Foxp3(+) T cells in vivo. Mechanistically, in vitro conversion of naive CD4(+) T cells into iTreg was crucially dependent on c-Rel-mediated synthesis of endogenous IL-2. The addition of exogenous IL-2 was sufficient to rescue the development of c-Rel-deficient iTreg. Thus, c-Rel is essential for the development of Foxp3(+) Treg but not for T(H)17 cells via regulating the production of IL-2.
Visekruna
Alexander
A
Institute for Medical Microbiology and Hygiene, University of Marburg, Marburg, Germany. alexander.visekruna@staff.uni-marburg.de
Huber
Magdalena
M
Hellhund
Anne
A
Bothur
Evita
E
Reinhard
Katharina
K
Bollig
Nadine
N
Schmidt
Nicole
N
Joeris
Thorsten
T
Lohoff
Michael
M
Steinhoff
Ulrich
U
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology*; D002469:Cell Separation; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000276:immunology*; D020381:Interleukin-17 / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D020569:Proto-Oncogene Proteins c-rel / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology* / Q000276:immunology
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D020381:Interleukin-17; D007376:Interleukin-2; D020569:Proto-Oncogene Proteins c-rel