Interleukin-2 immunotherapy reveals human regulatory T cell subsets with distinct functional and tissue-homing characteristics

被引：4

作者：

Raeber, Miro E. ^{[1
,2
,3
]}

Caspar, Dominic P. ^{[1
]}

Zurbuchen, Yves ^{[1
]}

Guo, Nannan ^{[4
]}

Schmid, Jonas ^{[1
]}

Michler, Jan ^{[5
]}

Martin, Alina C. ^{[1
]}

Steiner, Urs C. ^{[1
]}

Moor, Andreas E. ^{[5
]}

Koning, Frits ^{[4
]}

Boyman, Onur ^{[1
,2
,3
,6
]}

机构：

[1] Univ Hosp Zurich, Dept Immunol, CH-8091 Zurich, Switzerland

[2] Univ Zurich, Fac Med, CH-8032 Zurich, Switzerland

[3] Univ Zurich, Ctr Human Immunol, CH-8006 Zurich, Switzerland

[4] Leiden Univ, Dept Immunol, Med Ctr, NL-2300 RC Leiden, Netherlands

[5] Swiss Fed Inst Technol, Dept Biosyst Sci & Engn, CH-4056 Basel, Switzerland

[6] Univ Zurich, Fac Sci, CH-8057 Zurich, Switzerland

来源：

IMMUNITY | 2024年 / 57卷 / 09期

基金：

瑞士国家科学基金会;

关键词：

LOW-DOSE INTERLEUKIN-2; SYSTEMIC-LUPUS-ERYTHEMATOSUS; THERAPY; IL-2; MECHANISMS; AUTOIMMUNE; DISEASE; DIFFERENTIATION; VISUALIZATION; STIMULATION;

D O I：

10.1016/j.immuni.2024.07.016

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：2232 / 2250.e10

页数：30

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