Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge

Astrid L. Voskamp, Tamar Tak, Maarten L. Gerdes, Roberta Menafra, Ellen Duijster, Szymon M. Kielbasa, Tom Groot Kormelink, Koen A. Stam, Oscar R.J. van Hengel, Nicolette W. de Jong, Rudi W. Hendriks, Susan L. Kloet, Maria Yazdanbakhsh, Esther C. de Jong, Roy Gerth van Wijk, Hermelijn H. Smits*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Innate mononuclear phagocytic system (MPS) cells preserve mucosal immune homeostasis. We investigated their role at nasal mucosa following allergen challenge with house dust mite. We combined single-cell proteome and transcriptome profiling on nasal immune cells from nasal biopsies cells from 30 allergic rhinitis and 27 non-allergic subjects before and after repeated nasal allergen challenge. Biopsies of patients showed infiltrating inflammatory HLA-DRhi/CD14+ and CD16+ monocytes and proallergic transcriptional changes in resident CD1C+/CD1A+ conventional dendritic cells (cDC)2 following challenge. In contrast, non-allergic individuals displayed distinct innate MPS responses to allergen challenge: predominant infiltration of myeloid-derived suppressor cells (MDSC: HLA-DRlow/CD14+ monocytes) and cDC2 expressing inhibitory/tolerogenic transcripts. These divergent patterns were confirmed in ex vivo stimulated MPS nasal biopsy cells. Thus, we identified not only MPS cell clusters involved in airway allergic inflammation but also highlight novel roles for non-inflammatory innate MPS responses by MDSC to allergens in non-allergic individuals. Future therapies should address MDSC activity as treatment for inflammatory airway diseases.

Original languageEnglish
Article numbere20221111
JournalThe Journal of experimental medicine
Volume220
Issue number9
DOIs
Publication statusPublished - 4 Sept 2023

Bibliographical note

Funding Information:
We thank staff from the flow core facility for help with FACS sorting of cells from nasal biopsies prior to single-cell transcriptomics and with setting up and maintaining the spectral and mass cytometers. This work was supported by consortium grants from the Netherlands Lung Foundation (AWWA-12017001 and 5.1.15.015), Top Sector Life Sciences & Health-Top Consortia for Knowledge and Innovation project DC4Balance LSHM18056-SGF, and the Netherlands Science Council (40-43500-98-4066 and vidi-91714352).

Funding Information:
This work was supported by consortium grants from the Netherlands Lung Foundation (AWWA-12017001 and 5.1.15.015), Top Sector Life Sciences & Health - Top Consortia for Knowledge and Innovation project DC4Balance LSHM18056-SGF, and the Netherlands Science Council (40-43500-98-4066 and vidi-91714352).

Publisher Copyright:
© 2023 Voskamp et al.

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