重度喘息治療後も炎症性細胞が血中に残存(Inflammatory cells remain in the blood after treatment of severe asthma)

2025-06-26 カロリンスカ研究所(KI)

<関連情報>

• https://news.ki.se/inflammatory-cells-remain-in-the-blood-after-treatment-of-severe-asthma
• https://onlinelibrary.wiley.com/doi/10.1111/all.16633

重症喘息におけるメポリズマブまたはデュピルマブ治療中の2型リンパ球動態の高次元解析 High-Dimensional Analysis of Type 2 Lymphocyte Dynamics During Mepolizumab or Dupilumab Treatment in Severe Asthma

Lorenz Wirth, Whitney Weigel, Christopher T. Stamper, Johan Kolmert, Sabrina de Souza Ferreira, Quirin Hammer, Maria Sparreman Mikus, Jakob Theorell, Lars Andersson I …
Allergy  Published: 26 June 2025
DOI:https://doi.org/10.1111/all.16633

Graphical Abstract

We profiled PBMCs in severe asthma patients at baseline and after initiating treatment with mepolizumab or dupilumab. Mepolizumab treatment increases ILC2, Th2, and Tc2 cell frequencies, skewing ILC2 towards CD117^low and Th2/Tc2 cells towards a central memory phenotype. Type 2 lymphocytes in mepolizumab-treated patients display altered expression of tissue-homing receptors and produce more type 2 cytokines in vitro. CXCR4, C-X-C Motif Chemokine Receptor 4; GPR183, G-Protein Coupled Receptor 183; ILC2, Type 2 Innate Lymphoid Cell; scRNAseq, Single-Cell RNA Sequencing; Tc2, Type 2 Cytotoxic T Cell; Th2, Type 2 T Helper Cell.

ABSTRACT

Background

Although the type 2 biologics mepolizumab and dupilumab show clinical efficacy in severe asthma, their influence on circulating lymphocytes is largely unknown. Here, we studied their impact on type 2 lymphocytes in severe asthma.

Methods

We performed high-parameter flow cytometry analysis of peripheral blood mononuclear cells from 40 patients with severe asthma before, and after 4 and 12 months of mepolizumab (n = 33) or dupilumab (n = 7) treatment, focusing on type 2 lymphocytes. Additionally, we performed single-cell RNA sequencing (scRNA-seq) (n = 3) and stimulation experiments of type 2 lymphocytes (n = 3) to explore transcriptional and functional changes associated with mepolizumab treatment.

Results

Mepolizumab treatment increased circulating type 2 innate lymphoid cell (ILC2), type 2 T helper (Th2) and type 2 cytotoxic (Tc2) cell frequencies, skewing ILC2 towards a CD117^low signature with high CD62L expression, and Th2/Tc2 cells towards a CD45RA^–CD62L⁺ central memory phenotype. Dupilumab-treated patients also showed increased frequencies of total ILC2 and CD117^low ILC2. Mepolizumab treatment reduced the expression of tissue homing receptors CXCR4 in ILC2, and GPR183 in ILC2, Th2, and Tc2 cells while enhancing their type 2 cytokine producing capability in response to alarmins.

Conclusion

Mepolizumab increases the frequencies of circulating ILC2, Th2, and Tc2 cells, with reduced tissue homing receptor expression but increased type 2 cytokine production potential. This reveals a potentially new mechanism for how mepolizumab reduces airway inflammation by re-directing trafficking of inflammatory type 2 lymphocytes away from airway-homing, with implications for the possibility of achieving biologics-free remission in asthma.