Other
17 Authors
- Muniz GJ,
- Chaturvedi P,
- Li L,
- Zhu X,
- Spanoudis C,
- You L,
- Kong L,
- Wong HC,
- George V,
- Liu B,
- Li Q,
- Wang Z,
- Shrestha N,
- Echeverri C,
- Rhode PR,
- Egan JO,
- Gilkes C
| First Author | Zhu X | Year | 2023 |
| Journal | Front Immunol | Volume | 14 |
| Pages | 1114802 | PubMed ID | 36761778 |
| Mgi Jnum | J:336263 | Mgi Id | MGI:7433489 |
| Doi | 10.3389/fimmu.2023.1114802 | Citation | Zhu X, et al. (2023) A novel interleukin-2-based fusion molecule, HCW9302, differentially promotes regulatory T cell expansion to treat atherosclerosis in mice. Front Immunol 14:1114802 |
| abstractText | Atherosclerosis is a chronic inflammatory disease caused by deposition of oxidative low-density lipoprotein (LDL) in the arterial intima which triggers the innate immune response through myeloid cells such as macrophages. Regulatory T cells (Tregs) play an important role in controlling the progression or regression of atherosclerosis by resolving macrophage-mediated inflammatory functions. Interleukin-2 (IL-2) signaling is essential for homeostasis of Tregs. Since recombinant IL-2 has an unfavorable pharmacokinetic profile limiting its therapeutic use, we constructed a fusion protein, designated HCW9302, containing two IL-2 domains linked by an extracellular tissue factor domain. We found that HCW9302 exhibited a longer serum half-life with an approximately 1000-fold higher affinity for the IL-2Ralpha than IL-2. HCW9302 could be administered to mice at a dosing range that expanded and activated Tregs but not CD4(+) effector T cells. In an ApoE(-/-) mouse model, HCW9302 treatment curtailed the progression of atherosclerosis through Treg activation and expansion, M2 macrophage polarization and myeloid-derived suppressor cell induction. HCW9302 treatment also lessened inflammatory responses in the aorta. Thus, HCW9302 is a potential therapeutic agent to expand and activate Tregs for treatment of inflammatory and autoimmune diseases. |
