Expression of CD25 in human lung mast cells and its regulation by IL-33
(2026) In Journal of Allergy and Clinical Immunology 157(6). p.1442-1449- Abstract
Background: Expression of CD25, the IL-2 receptor alpha chain, on human mast cells is primarily associated with aberrant mast cells in clonal mast cell disorders. However, the regulation of CD25 expression in normal, mature tissue-resident mast cells remains poorly understood. Objective: IL-33 is a key modulator of immune responses, including in lung inflammatory conditions. Because mast cells are prominent IL-33 receptor–expressing cells, we investigated the effect of IL-33 on CD25 expression in purified human lung mast cells (HLMCs). Methods: Purified HLMCs were stimulated with IL-33 and the transcriptional responses measured by RNA sequencing. The expression of the IL-2 receptor subunits CD25 (IL2RA), CD122 (IL2RB), and CD132 (IL2RG)... (More)
Background: Expression of CD25, the IL-2 receptor alpha chain, on human mast cells is primarily associated with aberrant mast cells in clonal mast cell disorders. However, the regulation of CD25 expression in normal, mature tissue-resident mast cells remains poorly understood. Objective: IL-33 is a key modulator of immune responses, including in lung inflammatory conditions. Because mast cells are prominent IL-33 receptor–expressing cells, we investigated the effect of IL-33 on CD25 expression in purified human lung mast cells (HLMCs). Methods: Purified HLMCs were stimulated with IL-33 and the transcriptional responses measured by RNA sequencing. The expression of the IL-2 receptor subunits CD25 (IL2RA), CD122 (IL2RB), and CD132 (IL2RG) was quantified by real-time quantitative PCR and flow cytometry. IL2RA expression was further examined in publicly available single-cell RNA sequencing datasets, and in situ CD25 protein expression on HLMCs was assessed in human lung tissue by immunofluorescence staining. Results: IL-33 robustly induced the expression of CD25 and CD132 in HLMCs without a corresponding upregulation of CD122, resulting in absent IL-2–mediated signaling despite enhanced IL-2 binding via CD25. Single-cell RNA sequencing data identified IL2RA+ mast cells as a distinct subpopulation with enriched IL-33 response signatures and upregulation of genes linked to immune signaling and inflammatory pathways. CD25-positive HLMCs were also detected in situ, displaying substantial heterogeneity in expression levels and spatial distribution. Conclusions: CD25 expression in HLMCs is upregulated by IL-33 and is dynamically regulated in human lung tissues.
(Less)
- author
- organization
- publishing date
- 2026-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- CD25, COPD, IL-2 receptor, IL-33, Lung mast cells, pulmonary emphysema
- in
- Journal of Allergy and Clinical Immunology
- volume
- 157
- issue
- 6
- pages
- 8 pages
- publisher
- Elsevier
- external identifiers
-
- pmid:41825599
- scopus:105035334267
- ISSN
- 0091-6749
- DOI
- 10.1016/j.jaci.2026.03.003
- language
- English
- LU publication?
- yes
- id
- 759af967-b72e-4754-8875-d91852292b2f
- date added to LUP
- 2026-06-12 11:33:46
- date last changed
- 2026-06-26 12:18:32
@article{759af967-b72e-4754-8875-d91852292b2f,
abstract = {{<p>Background: Expression of CD25, the IL-2 receptor alpha chain, on human mast cells is primarily associated with aberrant mast cells in clonal mast cell disorders. However, the regulation of CD25 expression in normal, mature tissue-resident mast cells remains poorly understood. Objective: IL-33 is a key modulator of immune responses, including in lung inflammatory conditions. Because mast cells are prominent IL-33 receptor–expressing cells, we investigated the effect of IL-33 on CD25 expression in purified human lung mast cells (HLMCs). Methods: Purified HLMCs were stimulated with IL-33 and the transcriptional responses measured by RNA sequencing. The expression of the IL-2 receptor subunits CD25 (IL2RA), CD122 (IL2RB), and CD132 (IL2RG) was quantified by real-time quantitative PCR and flow cytometry. IL2RA expression was further examined in publicly available single-cell RNA sequencing datasets, and in situ CD25 protein expression on HLMCs was assessed in human lung tissue by immunofluorescence staining. Results: IL-33 robustly induced the expression of CD25 and CD132 in HLMCs without a corresponding upregulation of CD122, resulting in absent IL-2–mediated signaling despite enhanced IL-2 binding via CD25. Single-cell RNA sequencing data identified IL2RA+ mast cells as a distinct subpopulation with enriched IL-33 response signatures and upregulation of genes linked to immune signaling and inflammatory pathways. CD25-positive HLMCs were also detected in situ, displaying substantial heterogeneity in expression levels and spatial distribution. Conclusions: CD25 expression in HLMCs is upregulated by IL-33 and is dynamically regulated in human lung tissues.</p>}},
author = {{Gong, Yitao and Atanasoai, Ionut and Siddhuraj, Premkumar and Johnsson, Anna Karin and Peng, Yueling and Al-Ameri, Mamdoh and Sachs, Erik and Vali, Kasra and Adner, Mikael and Säfholm, Jesper and Erjefält, Jonas S. and Nilsson, Gunnar P. and Rönnberg, Elin}},
issn = {{0091-6749}},
keywords = {{CD25; COPD; IL-2 receptor; IL-33; Lung mast cells; pulmonary emphysema}},
language = {{eng}},
number = {{6}},
pages = {{1442--1449}},
publisher = {{Elsevier}},
series = {{Journal of Allergy and Clinical Immunology}},
title = {{Expression of CD25 in human lung mast cells and its regulation by IL-33}},
url = {{http://dx.doi.org/10.1016/j.jaci.2026.03.003}},
doi = {{10.1016/j.jaci.2026.03.003}},
volume = {{157}},
year = {{2026}},
}