Low-dose IL-2 enhances the generation of IL-10-producing immunoregulatory B cells

Journal article

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

Authors: Inaba, A; Tuong, ZK; Zhao, TX; Stewart, AP; Mathews, R

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Nature Research
• Journal: Nature Communications
• Volume: 14
• Issue: 1
• Pages: 2071-2071
• Article number: 2071
• Publication date: 2023-04-12
• DOI: 10.1038/s41467-023-37424-w
• EISSN: 2041-1723
• ISSN: 2041-1723
• Language: English
• Keywords: Secretion; IL-2 receptor; Immune system; Antibody; Gene; Molecular biology; Immunology; Regulatory B cells; Genetics; Repressor; Gene expression; B cell; Endocrinology; Interleukin 10; Cell biology; T cell; Biology