Foxp3-dependent microRNA155 confers competitive fitness to regulatory T cells through targeting SOCS1

By Li-Fan Lu, T. Thai, D. Calado, A. Chaudhry, Masato Kubo, Kentaro Tanaka, Gabriel B. Loeb, Hana Lee, A. Yoshimura, K. Rajewsky and 1 more. Immunity, 2009

807 citations recorded by the source corpus.

Foxp3+ regulatory T (TR) cells limit pathogenic immune responses to self and foreign antigens. An essential role for microRNA (miRNA) in the maintenance and function of TR cells, revealed by the TR-specific Dicer ablation, raised a question as to a specific miRNA contribution. We found that Foxp3 controls the elevated miR155 expression required for maintaining TR proliferative activity and numbers under non-lymphopenic conditions. Moreover, miR155 deficiency in TR cells results in increased SOCS1 expression accompanied by impaired STAT5 activation in response to limiting amounts of IL-2. Our studies suggest Foxp3-dependent regulation of miR155 maintains competitive fitness of TR subset by targeting SOCS1, and provide an experimental support for a proposed role for miRNAs in ensuring the robustness of cellular phenotypes.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/048674e5c0eacd686a777cc2031e2f8a031b4640

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Immunology

Citations in the corpus

Akt1 controls macrophage response to LPS by regulating microRNAs (2009, background): “MiR155 also targets and suppresses SOCS1, a critical regulator of STAT signaling, in regulatory T cells (Lu et al., 2009) and the inositol phosphatase SHIP1 (O’Connell et al., 2009).”
Non-coding RNAs in disease: from mechanisms to therapeutics (2023, neutral): “In addition, miR-155 is required for optimal proliferation of regulatory T cells in vitro 314 , which suggests an important role in regulating T cell expansion.”
The role of JAK-STAT signaling pathway and its regulators in the fate of T helper cells (2017, background): “SOCS1 negatively regulate the number of Treg cells, but has an essential role in Treg functions [63].”
MicroRNA-155 promotes autoimmune inflammation by enhancing inflammatory T cell development (2010, background): “The fitness of T regulatory cells is influenced by direct repres- sion of suppressor of cytokine signaling 1 (SOCS1) by miR- 155 (Lu et al., 2009).”
Metazoan MicroRNAs (2018, background): “…Impaired development and function of B cells, T cells, and dendritic cells (Rodriguez et al., 2007; Thai et al., 2007; Kohlhaas et al., 2009; Lu et al., 2009; O’Connell et al., 2010; Dunand-Sauthier et al., 2011); perturbed function of macrophages and mast cells (O’Connell et al., 2009;…”
MicroRNAs in development and disease. (2011, background): “miR-155 is regulated by Foxp3 and was indeed confirmed necessary for the optimal proliferation of thymic and peripheral Foxp3 T-reg cells (389).”
Inositol phosphatase SHIP1 is a primary target of miR-155 (2009, background): “SOCS1 targeting by miR-155 has just recently been shown to impact T-regulatory cell homeostasis (49).”
Function of miR-146a in controlling Treg cell-mediated regulation of Th1 responses (2010, positive): “This is likely due to augmented IL-2R/Stat5 signaling (Figure S4; Lu et al., 2009; Zhan et al., 2009).”
MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. (2010, methodology): “While we were preparing this article, an independent article reported that socs1 is a target of miR-155 in T regulatory cells (25), confirming that socs1 is an authentic target of miR-155.”
Regulatory T Cells: Mechanisms of Differentiation and Function (2012, background): “Furthermore, many of Treg cell–specific miRNAs are expressed in Treg cells in a Foxp3-dependent manner (145, 146, 169).”
Plasticity of CD4+ T cell lineage differentiation. (2009, background): “IL-12Rb2 induction is dependent on T-bet activation through IFN-g and Stat1 signaling (Mullen et al., 2001; Afkarian et al., 2002).”