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Luciana Molinero, Michelle Miller, Mona Mashayekhi, Luqiu Chen, Ping Zhou, Nicole Tramontini, Monica Michelotti, Xindong Liu, Xiaoping Zhu, Maria-Luisa Alegre, NF-κB controls IL-7 receptor expression in T cells (P6295), The Journal of Immunology, Volume 190, Issue Supplement_1, May 2013, Page 184.9, https://doi.org/10.4049/jimmunol.190.Supp.184.9
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Abstract
IL-7 and tonic TCR signaling control naïve T cell homeostasis. The transcription factor NF-κB plays a key role during T cell activation, proliferation and survival, but little is known on the role of basal NF-κB in quiescent T cells. Using mice bearing NF-κB impaired T cells (IκBαΔN), we show that basal levels of NF-κB signaling in naïve T cells are required for cell survival both in vivo and in vitro. In vitro, IκBαΔN T cells display reduced survival to IL-7, IL-7-mediated STAT5 phosphorylation and Bcl2 upregulation. Indeed, protein levels of IL-7Rα, but not common γc subunit (CD132), are markedly reduced in IκBαΔN naïve T cells. Assessing mice deficient for NF-κB1 and NF-κB2 subunits, canonical (NF-κB1) but not alternate (NF-κB2) NF-κB pathway is required for IL7Rα expression in T cells. Conversely, constitutive activation of NF-κB in T cells (Lck-Cre x IKKβCA) enhances IL-7Rα expression and IL-7 induced T cell survival. RelA/p65 and NF-κB1/p50 might control transcription through a κB binding region located 3.5 kb upstream of il7r gene, as assessed by EMSA and chromatin immunoprecipitation. Notably, using a NF-κB pharmacological inhibitor we show that NF-κB also controls IL-7Rα expression in human T cells. Taken together, our data suggest that NF-κB regulates il7r transcription both in mice and human, therefore affecting homeostasis of naive T cells.
