Prostaglandin E2 restrains human Treg cell differentiation via E prostanoid receptor 2-protein kinase A signaling

Li, Hui; Chen, Haiying; Liu, Wenxuan; Jia, Xianxian; Zhang, Jingge; Ma, Chunling; Zhang, Xiaojing; Feng, Yu; Cong, Bin

doi:10.1016/j.imlet.2017.09.009

Cited by 28 publications

(28 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In vitro, PGE 2 can upregulate Foxp3, a lineage specification marker expressed by Treg [56], consistent with cancer models where PGE 2 produced in the tumor microenvironment can polarize T cells toward the iTreg phenotype to suppress anti-tumor responses [57,58]. However, in another in vitro study, PGE 2 was shown inhibit iTreg differentiation via EP2 the receptor [59], emphasizing differential roles that depend on the tissue environment.…”

Section: Pge 2 Regulation Of Lymphoid-derived Cellssupporting

confidence: 61%

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

Wei

Gronert

2019

Trends in Biochemical Sciences

View full text Add to dashboard Cite

Eicosanoids and specialized proresolving mediators (SPM) regulate leukocyte function and inflammation. They are ideally positioned at the interphase of innate and adaptive immune responses when lymphocytes interact with leukocytes. Receptors for LTB4, PGE2 and SPM are expressed in lymphocytes. Evidence points toward an essential role of these lipid mediators for directly regulating lymphocyte functions. SPMs, which include lipoxins, demonstrate comprehensive protective actions with lymphocytes. LTB4 and PGE2 regulation of lymphocyte is diverse and depends on the interaction of lymphocytes with other cells. Importantly, both LTB4 and PGE2 are essential regulators of T cell anti-tumor activity. These lipid mediators are attractive therapeutic targets to control dysregulated innate and adaptive immune responses, promote lymphocyte antitumor activity and prevent tumor immune evasion.

show abstract

Section: Pge 2 Regulation Of Lymphoid-derived Cellssupporting

confidence: 61%

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

Wei

Gronert

2019

Trends in Biochemical Sciences

View full text Add to dashboard Cite

show abstract

“…PGE 2 plays a role in the differentiation of various cell types, such as regulatory T cells [33], osteoblasts [34], and neurons [35]. Our previous study reported that PGE 2 , which is increased in the spinal cord of ALS patients [36] and model mice [30], induced morphological differentiation of undifferentiated NSC-34 cells [16].…”

Section: Discussionmentioning

confidence: 97%

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

Nango

Kosuge

Yoshimura

et al. 2020

Cells

View full text Add to dashboard Cite

Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E2 promotes neurite outgrowth in NSC-34 cells, which are a model for motor neuron development. However, the effects of other prostaglandins on neuronal differentiation are poorly understood. The present study investigated the effect of prostaglandin D2 (PGD2) on neuritogenesis in NSC-34 cells. Exposure to PGD2 resulted in increased percentages of neurite-bearing cells and neurite length. Although D-prostanoid receptor (DP) 1 and DP2 were dominantly expressed in the cells, BW245C (a DP1 agonist) and 15(R)-15-methyl PGD2 (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD2 was converted to 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) under cell-free conditions. Exogenously applied 15d-PGJ2 mimicked the effect of PGD2 on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor–gamma (PPARγ) antagonist, suppressed PGD2-induced neurite outgrowth. Moreover, PGD2 and 15d-PGJ2 increased the protein expression of Islet-1 (the earliest marker of developing motor neurons), and these increases were suppressed by co-treatment with GW9662. These results suggest that PGD2 induces neuritogenesis in NSC-34 cells and that PGD2-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ2.

show abstract

“…On the one hand, it was shown that PGE2 upregulates both mRNA and protein expression of Foxp3, induces the regulatory phenotype in CD4 + CD25 − cells and increases suppressive functions of isolated human CD4 + CD25 +++ Tregs [49]. On the other, PGE2 can inhibit the differentiation of Treg mediated through the EP2-cAMP/PKA signaling pathway [50]. In our work, we did not observe any significant differences in CD4 + FOXP3 + numbers depending on the kind of drugs taken in the OA patients' group.…”

Section: Discussionmentioning

confidence: 99%

CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired

Massalska

Radzikowska

Kuca-Warnawin

et al. 2020

Cells

View full text Add to dashboard Cite

There is evolving evidence that dysregulation of immune homeostasis in the bone marrow (BM) adjacent to the inflamed joints is involved in the pathogenesis of. In this study, we are addressing the phenotype and function of regulatory T cells (Tregs) residing in the BM of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). BM and peripheral blood samples were obtained from RA and OA patients undergoing hip replacement surgery. The number and phenotype of Tregs were analyzed by flow cytometry and immunohistochemistry. The function of Tregs was investigated ex vivo, addressing their suppressive activity on effector T cells. [3H]-Thymidine incorporation assay and specific enzyme-linked immunosorbent assay were used for quantification of cell proliferation and pro-inflammatory (TNF, IFN-γ) cytokine release, respectively. Significantly lower numbers of CD4+FOXP3+ T cells were found in the BM of patients with RA compared to control patients with OA. High expression of CD127 (IL-7α receptor) and relatively low expression of CXCR4 (receptor for stromal cell-derived factor CXCL12) are characteristics of the CD4+FOXP3+ cells residing in the BM of RA patients. The BM-resident Tregs of RA patients demonstrated a limited suppressive activity on the investigated immune response. Our results indicate that the reduced number and impaired functional properties of CD4+FOXP3+ T cells present in the BM of RA patients may favor the inflammatory process, which is observed in RA BM.

show abstract

Prostaglandin E2 restrains human Treg cell differentiation via E prostanoid receptor 2-protein kinase A signaling

Cited by 28 publications

References 46 publications

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

Eicosanoid and Specialized Proresolving Mediator Regulation of Lymphoid Cells

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

CD4+FOXP3+ T Cells in Rheumatoid Arthritis Bone Marrow Are Partially Impaired

Contact Info

Product

Resources

About