mProX™ Human C3AR1 Stable Cell Line

Medof ME, et al. "Disabled C3ar1/C5ar1 Signaling in Foxp3+ T Regulatory Cells Leads to TSDR ." Journal of immunology (Baltimore, Md. : 1950), 2023.
The demethylation process of the T regulatory cell (Treg)-specific demethylation region (TSDR) of the Foxp3 gene is crucial for maintaining stability in Foxp3+ Tregs. However, the exact cellular signaling that controls this epigenetic state is not well understood. This study shows that suppressed C3a and C5a receptor (C3ar1/C5ar1) signaling in murine Tregs plays a necessary role in this process. Mice lacking both C3ar1 and C5ar1 expressed increased levels of suppressor of cytokine signaling 1/2/3 and vitamin C stabilization. They also showed enhanced expression of TET 1, 2, and 3, all of which are associated with Treg stability. Additionally, these cells lacked BRD4 signaling, which is known to promote Th17 cell differentiation. When orally induced OVA-specific C3ar1-/-C5ar1-/- Foxp3+ OT-II Tregs were transferred to OVA-immunized wild-type recipients, they maintained>90% Foxp3 expression for 4 months. However, CD55-/- (DAF-/-) Foxp3+ OT-II Tregs, which have increased C3ar1/C5ar1 signaling, lost>75% of Foxp3 expression after 14 days. After 4 months in vivo, the C3ar1-/-C5ar1-/- Foxp3+ OT-II Tregs retained Foxp3 expression even after OVA challenge and produced high levels of TGF-beta and IL-10. The demethylation of their TSDR was comparable to that of thymic Tregs, and they showed nuclear translocation of NFAT and NF-kappaB, which are known to stabilize thymic Tregs by inducing hairpin looping of the TSDR to the Foxp3 promoter. Therefore, impaired C3ar1/C5ar1 signaling in CD4+ cells triggers a series of events that lead to demethylation of the Foxp3 TSDR.
Pubmed: 37756526   DOI: 10.4049/jimmunol.2300184

Wang X, et al. "The effect of butylphthalide on improving the neurological function of patients ." Medicine, 2023.
Butylphthalide has been shown to improve blood circulation in patients with acute cerebral infarction. The role of Complement 3a receptor 1 (C3aR1) in the regulation of innate immune response and pathogen monitoring has been closely associated with the pathophysiological processes of breast cancer, neurogenesis, and lipid catabolism. This study investigated the therapeutic effects of butylphthalide on the neurological function of patients with acute anterior circulation cerebral infarction following mechanical thrombectomy. The study also aimed to evaluate the relationship between butylphthalide and serum C3aR1 levels in improving neurological function after thrombectomy. A retrospective study was performed on 288 patients with acute anterior circulation cerebral infarction who underwent mechanical thrombectomy as their first-time treatment. The patients were divided into a butylphthalide group and a control group based on their treatment methods. The National Institutes of Health Stroke Scale (NIHSS) was used to assess neurological function treatment efficacy, and the modified Rankin Scale (mRS) was used to measure neurological function status three months post-surgery. The serum C3aR1 levels were determined using the enzyme-linked immunosorbent assay (ELISA) method. The butylphthalide group showed a significantly higher NIHSS efficacy (94.44%) compared to the control group (72.22%) two weeks after thrombus removal (P< .001). Three months post-surgery, the butylphthalide group had a significantly lower mRS score (P = .001) and a higher excellent and good rate (P< .001) compared to the control group. The serum C3aR1 levels in the butylphthalide group were significantly lower than the control group at both two weeks and three months post-surgery (P< .001). The serum C3aR1 levels were positively correlated with NIHSS efficacy (R = 0.815, P = .004) and mRS score (R = 0.774, P = .007). These results suggest that butylphthalide can enhance the therapeutic effects on neurological function in patients with acute anterior circulation cerebral infarction after mechanical thrombus removal. Additionally, the serum C3aR1 levels are closely related to neurotherapy efficacy and the recovery of neurological function in patients, providing a possible indicator for monitoring patient recovery.
Pubmed: 37653792   DOI: 10.1097/MD.0000000000034616