Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells

Chen, Haiying; Jin, Qin; Wei, Ping; Zhang, Jingge; Li, Qiaoxia; Fu, Lihong; Li, Shujin; Ma, Chunling; Cong, Bin

doi:10.1016/j.plefa.2009.01.006

Cited by 79 publications

(65 citation statements)

References 33 publications

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“…2). This suppressive effect of PGE 2 on Th17 cell differentiation by TGF-b and IL-6 was also reported by Chen et al (12). On the other hand, PGE 2 concentration-dependently expanded Th17 cell population in the presence of IL-23 (11) (Fig.…”

Section: Facilitation Of Th17 Expansion By Pge 2 In Vitrosupporting

confidence: 84%

Emerging roles of prostanoids in T cell‐mediated immunity

2010

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SummaryThree distinct subsets of T helper (Th) cells, Th1, Th2, and Th17, not only contribute to host defense against pathogens, but also cause many types of immune diseases. Differentiation and functions of these T cell subsets are mainly regulated by specific cytokines. Intriguingly, recent studies have revealed that prostanoids including various types of prostaglandins (PGs) and thromboxane (TX) are also involved in these processes. Prostanoids exert their actions by binding to their specific receptors. They include PGD receptor, EP1, EP2, EP3, and EP4 subtypes of PGE receptor, PGF receptor, PGI receptor, and TX receptor. From many in vitro findings, prostanoids, especially PGE 2 , were traditionally believed to be an immunosuppressant. However, studies using mice deficient in each type or subtype of prostanoid receptors and their selective agonists and antagonists have revealed that prostanoids collaborate with cytokines, and critically regulate T cell proliferation, differentiation and functions. Recent studies have revealed that PGE 2 facilitates Th1 cell differentiation and Th17 cell expansion in collaboration with IL-12 and IL-23, respectively, and that these PGE 2 actions contribute to development of immune diseases mediated by these Th subsets. Furthermore, studies using the receptor-deficient mice have also revealed that other prostanoids including PGD 2 and PGI 2 contribute to regulation of immune diseases of the Th2 type such as allergic asthma. These findings shed a new light on the roles of prostanoids in T cell-mediated immunity and immune diseases. IUBMBIUBMB Life, 62(8): 591-596, 2010

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Section: Facilitation Of Th17 Expansion By Pge 2 In Vitrosupporting

confidence: 84%

Emerging roles of prostanoids in T cell‐mediated immunity

2010

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“…IL-6 and TGF-β are provided, for example, by DCs that have recognized apoptotic cells in tissue injury, and IL-23 is also provided by DCs after certain activation. We examined effects of PGE 2 on mouse Th17 development in vitro (19) and first found that PGE 2 potently suppresses Th17 differentiation from naïve T cells by IL-6 and TGF-β , which was consistent with the report by Chen et al (20). We then examined PGE 2 effects on Th17 expansion and found that PGE 2 facilitated Th17 expansion in the presence of IL-23.…”

Section: Pge 2 Action On Th17 Cell Expansion Revealedsupporting

confidence: 82%

Prostaglandin E2, an Immunoactivator

2010

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Abstract. Diseases caused by immune inflammation, such as rheumatoid arthritis, multiple sclerosis, and Crohn's disease, are intractable diseases to which novel therapeutics are highly demanded. Prostaglandin (PG) E 2 is the most ubiquitously produced PG with various actions. PGE 2 has been traditionally regarded as an immunosuppressant based on its inhibition of T cell activation in vitro. However, in vivo relevance of the immunosuppressant action of PGE 2 has remained obscure. Recently, several groups including ourselves have made unexpected findings that PGE 2 facilitates expansion of the Th17 subset of T helper cells of both human and mouse through elevation of cAMP via PGE receptors EP2 and EP4. We have further found that PGE 2 can induce and not suppress Th1 differentiation under certain conditions, again, through EP2 and EP4. Given the putative roles of these Th subsets in immune diseases such as the above, these findings suggest that, on the contrary to the traditional view, PGE 2 functions as a mediator of immune inflammation. Consistently, administration of an EP4 antagonist could suppress disease progression and development of antigen-specific Th17 cells in mice subjected to experimental allergic encephalomyelitis and contact hypersensitivity. In this perspective, we review these findings and discuss the prospect of EP4 antagonists as immunomodulatory drugs.

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“…PGF 2a is known to be crucial for polarization toward the Th17 cell type (44) by binding its receptor on CD4 + Th cells; in this way, it upregulates levels of RORgt transcription factor. In contrast, PGE 2 can act as a negative regulator of IL-17 production and RORgt mRNA levels in Th17 cells (45). Thus, the high levels of PGF 2a and low levels of PGE 2 that we observed may contribute to skewing toward Th17 polarization.…”

Section: Discussionmentioning

confidence: 52%

Antibody-Opsonized Bacteria Evoke an Inflammatory Dendritic Cell Phenotype and Polyfunctional Th Cells by Cross-Talk between TLRs and FcRs

Bakema

Tuk

Vliet

et al. 2015

The Journal of Immunology

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During secondary immune responses, Ab-opsonized bacteria are efficiently taken up via FcRs by dendritic cells. We now demonstrate that this process induces cross-talk between FcRs and TLRs, which results in synergistic release of several inflammatory cytokines, as well as altered lipid metabolite profiles. This altered inflammatory profile redirects Th1 polarization toward Th17 cell responses. Interestingly, GM-CSF–producing Th cells were synergistically evoked as well, which suggests the onset of polyfunctional Th17 cells. Synergistic cytokine release was dependent on activation via MyD88 and ITAM signaling pathways through TLRs and FcRs, respectively. Cytokine regulation occurred via transcription-dependent mechanisms for TNF-α and IL-23 and posttranscriptional mechanisms for caspase-1–dependent release of IL-1β. Furthermore, cross-talk between TLRs and FcRs was not restricted to dendritic cells. In conclusion, our results support that bacteria alone initiate fundamentally different immune responses compared with Ab-opsonized bacteria through the combined action of two classes of receptors and, ultimately, may refine new therapies for inflammatory diseases.

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Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells

Cited by 79 publications

References 33 publications

Emerging roles of prostanoids in T cell‐mediated immunity

Emerging roles of prostanoids in T cell‐mediated immunity

Prostaglandin E2, an Immunoactivator

Antibody-Opsonized Bacteria Evoke an Inflammatory Dendritic Cell Phenotype and Polyfunctional Th Cells by Cross-Talk between TLRs and FcRs

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