ReferenceID 5935
Paeoniflorin ameliorates murine lupus nephritis by increasing CD4+Foxp3+ Treg cells via enhancing mTNFα-TNFR2 pathway
Biochem Pharmacol
Treg cells are essential for re-establishing self-tolerance in lupus. However, given that direct Treg therapies may be inadequate to control autoimmunity and inflammation, a strategy of inducing or expanding endogenous T
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- Reference Id
- 5935
- Evidence Id
- 22525
- Core Evidence Id
- 22525
- Source Reference Id
- 5133
- Herb2 Reference Id
- HBREF005930
- Subject Paper Key
- HBIN038606_33513343
- Pubmed Id
- 33513343
- Doi
- 10.1016/j.bcp.2021.114434
- Paper Title
- Paeoniflorin ameliorates murine lupus nephritis by increasing CD4+Foxp3+ Treg cells via enhancing mTNFα-TNFR2 pathway
- Paper Abstract
- Treg cells are essential for re-establishing self-tolerance in lupus. However, given that direct Treg therapies may be inadequate to control autoimmunity and inflammation, a strategy of inducing or expanding endogenous Treg cells in vivo may be a good option. Macrophages are main tissue-infiltrating cells and play a role in promoting Treg differentiation while paeoniflorin (PF), a monoterpene glycoside, exhibits anti-inflammatory and immunoregulatory effects. Here, we studied the effects of PF on CD4+FoxP3+ Treg frequency and the potential mechanisms involving M2 macrophages. We demonstrated that PF ameliorated lupus nephritis in lupus-prone B6/gld mice by reducing urinary protein, serum creatinine and anti-dsDNA levels, diminishing renal cellular infiltration, improving renal immunopathology and downregulating renal gene and protein expressions of key cytokines, including IFN-gamma, IL-6, IL-12 and IL-23. PF also lowered the percentage of CD44highCD62Llow effector T cells while augmenting CD4+FoxP3+ Treg frequency in B6/gld mice. Importantly, PF increased TNFR2 expression on CD4+FoxP3+ Tregs, but not CD4+FoxP3- T cells, in vivo and in vitro. Furthermore, we found that CD206+ subset of F4/80+CD11b+ macrophages expressed a higher level of mTNF-alpha than their CD206- counterparts while PF increased mTNF-alpha expression on CD206+ macrophages in vitro and in vivo. In vitro studies showed that mTNF-alpha+ M2 macrophages were more potent in inducing Treg differentiation and proliferation than their mTNF-alpha- counterparts, whereas the effects of mTNF-alpha+ M2 macrophages were largely reversed by separation of M2 macrophages using a transwell or TNFR2-blocking Ab in the culture. Finally, PF also promoted in vitro Treg generation induced by M2 macrophages. Thus, we demonstrated that mTNFalpha-TNFR2 interaction is a new mechanism responsible for Treg differentiation mediated by M2 macrophages. We provided the first evidence that PF may be used to treat lupus nephritis.
- Journal
- Biochem Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; mtnf-alpha+ m2 macrophages
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Inflammation; Lupus; Lupus Nephritis; Pf Ameliorated Lupus Nephritis; Renal Immunopathology; Autoimmunity
- Paper Title Cn
- Paper Title En
- Paeoniflorin ameliorates murine lupus nephritis by increasing CD4+Foxp3+ Treg cells via enhancing mTNFα-TNFR2 pathway
- Bilingual Status
- semi_complete