Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA

Masuda, Kouji; Ripley, Barry; Nyati, Kishan Kumar; Dubey, Praveen; Zaman, Mohammad Mahabub-Uz; Hanieh, Hamza; Higa, Mitsuru; Yamashita, Kazuo; Standley, Daron M.; Mashima, Tsukasa; Katahira, Masato; Okamoto, Tomoyoshi; Matsuura, Yoshiharu; Takeuchi, Osamu; Kishimoto, Tadamitsu

doi:10.1084/jem.20151289

Cited by 85 publications

(114 citation statements)

References 51 publications

Supporting

Mentioning

103

Contrasting

Order By: Relevance

“…Arid5a deficiency was shown to inhibit the elevation of IL-6 serum levels in LPS-treated mice (11). Our recent study also showed an intrinsic role for Arid5a in T cells, where Arid5a was found to direct the differentiation of naive CD4 + T cells into inflammatory CD4 + T cells by the stabilization of STAT3 mRNA (12). Overall, these findings suggest Arid5a has an important immune regulatory function.…”

supporting

confidence: 58%

“…Arid family proteins are believed to have DNA-binding properties (18), but our group demonstrated that Arid5a can function as an RNA-binding protein (11,12). Thus, there is a possibility that Arid5a could regulate T-bet and IFN-γ transcriptionally, by activating their promoters, or posttranscriptionally, by activating their UTRs.…”

Section: Ifn-γ and T-bet Expression Is Significantly Decreased In Arimentioning

confidence: 98%

“…T-bet 3′UTR are critical for the stabilization of T-bet mRNA by Arid5a. Our group recently reported that Arid5a can recognize stem loop structure of the 3′UTR region of STAT3 mRNA (12). Thus, we looked for the stem loop-like structure in the ARE-containing fraction of the 3′UTR of T-bet (321-701).…”

Section: The Conserved Stem Loop Region Of the T-bet 3′utr (616-641) Ismentioning

confidence: 99%

“…AT-rich interactive domain containing protein 5a (Arid5a) is a member of the Arid protein family that functions as a unique RNA-binding protein (11,12). It is expressed highly in macrophage in response to LPS and controls posttranscriptional regulation of IL-6 by stabilizing IL-6 mRNA through binding to its 3′UTR (11).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Arid5a exacerbates IFN-γ–mediated septic shock by stabilizing T-bet mRNA

Zaman

Masuda

Nyati

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

Adenine-thymine (AT)-rich interactive domain containing protein 5a (Arid5a) is an RNA-binding protein that has been shown to play an important immune regulatory function via the stabilization of IL-6 and STAT3 mRNA. However, the role of Arid5a in the overwhelming and uncontrolled immune response that leads to septic shock is unknown. Here, we report that Arid5a-deficient mice are highly resistant to lipopolysaccharide (LPS)-induced endotoxic shock and secrete lower levels of major proinflammatory cytokines, including IFN-γ, IL-6, and TNF-α, than WT mice in response to LPS. Arid5a deficiency resulted in decreased levels of IFN-γ under Th1 cell conditions, in which T-box expressed in T cells (T-bet) mRNA expression was inhibited. Arid5a bound to the conserved stem loop structure of the 3′UTR of T-bet and stabilized its mRNA. Arid5a-deficient mice were also resistant to Propionibacterium acnes-primed LPS injection, which is considered to be a T-cell-mediated IFN-γ dependent endotoxic shock mouse model. Thus, regulation of IFN-γ by Arid5a via the stabilization of T-bet mRNA in Th1 cells contributes to the development of septic shock in mice. In addition, our previous study suggests that Arid5a control the IL-6 level in vivo in response to LPS by stabilization of IL-6 mRNA. We also observed that neutralization of IFN-γ and IL-6 significantly recovered the mice from endotoxic shock. Taken together, we conclude that Arid5a regulates the augmentation of IL-6 and IFN-γ in response to LPS, which possibly works synergistically for amplification of various other cytokines that ultimately cause the development of septic shock in mice.septic shock | Arid5a | IFN-γ | T-bet | IL-6

show abstract

supporting

confidence: 58%

Section: Ifn-γ and T-bet Expression Is Significantly Decreased In Arimentioning

confidence: 98%

Section: The Conserved Stem Loop Region Of the T-bet 3′utr (616-641) Ismentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Arid5a exacerbates IFN-γ–mediated septic shock by stabilizing T-bet mRNA

Zaman

Masuda

Nyati

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Collectively, these findings strongly suggest that modulation of IL-6 post-transcription is related to pathogenesis of sepsis. Additionally, we found the significant involvement of Arid5a in the differentiation of naïve helper T (Th) cells into Th17 cells in a murine experimental autoimmune encephalomyelitis (EAE) model, by controlling by stability of STAT3 mRNA [13].…”

mentioning

confidence: 96%

Implications of IL-6 Targeting Therapy for Sepsis

Kang¹,

Tanaka²,

Masuda³

et al. 2017

Immunotherapy

Self Cite

View full text Add to dashboard Cite

Post‐transcriptional control of immune responses and its potential application

Yoshinaga

Takeuchi

2019

Clin & Trans Imm

Self Cite

View full text Add to dashboard Cite

Inflammation is the host response against stresses such as infection. Although the inflammation process is required for the elimination of pathogens, uncontrolled inflammation leads to tissue destruction and inflammatory diseases. To avoid this, the inflammatory response is tightly controlled by multiple layers of regulation. Post‐transcriptional control of inflammatory mRNAs is increasingly understood to perform critical roles in this process. This is mediated primarily by a set of RNA binding proteins (RBPs) including tristetraprolin, Roquin and Regnase‐1, and RNA methylases. These key regulators coordinate the inflammatory response by modulating mRNA pools in both immune and local nonimmune cells. In this review, we provide an overview of the post‐transcriptional coordination of immune responses in various tissues and discuss how RBP‐mediated regulation of inflammation may be harnessed as a potential class of treatments for inflammatory diseases.

show abstract

Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA

Cited by 85 publications

References 51 publications

Arid5a exacerbates IFN-γ–mediated septic shock by stabilizing T-bet mRNA

Arid5a exacerbates IFN-γ–mediated septic shock by stabilizing T-bet mRNA

Implications of IL-6 Targeting Therapy for Sepsis

Post‐transcriptional control of immune responses and its potential application

Contact Info

Product

Resources

About