AI Article Synopsis
- Low-dose interleukin-2 (IL-2) immunotherapy shows promise for autoimmune diseases by stimulating regulatory T (Treg) cells, particularly in systemic lupus erythematosus (SLE) patients.
- A clinical trial revealed that low-dose IL-2 activates various immune cells, notably Treg cells with skin-homing capabilities, which interact with skin endothelial cells.
- Comprehensive analysis uncovered different subsets of Treg cells influenced by IL-2, indicating targetable immune responses in the treatment of SLE.
Article Abstract
Due to its stimulatory potential for immunomodulatory CD4 regulatory T (Treg) cells, low-dose interleukin-2 (IL-2) immunotherapy has gained considerable attention for the treatment of autoimmune diseases. In this investigator-initiated single-arm non-placebo-controlled phase-2 clinical trial of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE) patients, we generated a comprehensive atlas of in vivo human immune responses to low-dose IL-2. We performed an in-depth study of circulating and cutaneous immune cells by imaging mass cytometry, high-parameter flow cytometry, transcriptomics, and targeted serum proteomics. Low-dose IL-2 stimulated various circulating immune cells, including Treg cells with a skin-homing phenotype that appeared in the skin of SLE patients in close interaction with endothelial cells. Analysis of surface proteins and transcriptomes revealed different IL-2-driven Treg cell activation programs, including gut-homing CD38, skin-homing HLA-DR, and highly proliferative inflammation-homing CD38 HLA-DR Treg cells. Collectively, these data define the distinct human Treg cell subsets that are responsive to IL-2 immunotherapy.
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| http://dx.doi.org/10.1016/j.immuni.2024.07.016 | DOI Listing |
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