The development of inflammatory T(H)-17 cells requires interferon-regulatory factor 4.
Interferon-regulatory factor 4 (IRF4) is essential for the development of T helper type 2 cells. Here we show that IRF4 is also critical for the generation of interleukin 17-producing T helper cells (T(H)-17 cells), which are associated with experimental autoimmune encephalomyelitis. IRF4-deficient (Irf4(-/-)) mice did not develop experimental autoimmune encephalomyelitis, and T helper cells from such mice failed to differentiate into T(H)-17 cells. Transfer of wild-type T helper cells into Irf4(-/-) mice rendered the mice susceptible to experimental autoimmune encephalomyelitis. Irf4(-/-) T helper cells had less expression of RORgammat and more expression of Foxp3, transcription factors important for the differentiation of T(H)-17 and regulatory T cells, respectively. Altered regulation of both transcription factors contributed to the phenotype of Irf4(-/-) T helper cells. Our data position IRF4 at the center of T helper cell development, influencing not only T helper type 2 but also T(H)-17 differentiation.
Institut für Medizinische Mikrobiologie und Krankenhaushygiene, 35043 Marburg, Germany.
Anne
A
Brüstle
Sylvia
S
Heink
Magdalena
M
Huber
Christine
C
Rosenplänter
Christine
C
Stadelmann
Philipp
P
Yu
Enrico
E
Arpaia
Tak W
TW
Mak
Thomas
T
Kamradt
Michael
M
Lohoff
D000818:Animals; D002454:Cell Differentiation / Q000276:immunology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015870:Gene Expression; D015151:Immunoblotting; D007249:Inflammation / Q000276:immunology; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology* / Q000276:immunology; D000099218:Interferon Regulatory Factor-4
D051858:Forkhead Transcription Factors; D050835:Interferon Regulatory Factors; D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000099218:Interferon Regulatory Factor-4; C498833:Foxp3 protein, mouse; C539901:Rorc protein, mouse