Better safe than sorry: TOB1 employs multiple parallel regulatory pathways to keep Th17 cells quiet.
Th17 cells are key players in antibacterial and antifungal immunity, but have also been implicated in autoimmunity. Interestingly, Th17 cells poorly proliferate upon stimulation, a phenotype that was attributed to a decreased sensitivity to T-cell receptor (TCR) stimulation, and to low IL-2 production by Th17 cells. In this issue of the European Journal of Immunology, Santarlasci et al. [Eur. J. Immunol. 2014. 44: 654-661] shed further light on the molecular mechanism that keeps Th17 cells at bay. They identify the transcriptional regulator TOB1, which not only impairs IL-2 production in Th17 cells, but also blocks the expression of cell cycle genes. Strikingly, TOB1 suppresses Th17-cell proliferation through several pathways, including impaired signal transduction, transcription, and possibly also post-transcriptional regulation.
Department of Hematopoiesis, Sanquin Research/Landsteiner laboratory AMC, Amsterdam, The Netherlands.
Fiamma
F
Salerno
René A W
RA
van Lier
Monika C
MC
Wolkers
D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism*; D050830:L-Amino Acid Oxidase / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D058504:Th17 Cells / Q000276:immunology* / Q000378:metabolism*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; D011948:Receptors, Antigen, T-Cell; C098669:TOB1 protein, human; D025521:Tumor Suppressor Proteins; C105158:IL4I1 protein, human; D050830:L-Amino Acid Oxidase
Gene regulation; Proliferation; TOB1; Th17 cells