@article{8a19f8cca53545e59123a293316d6b69,
title = "Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge",
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.",
author = "Voskamp, {Astrid L.} and Tamar Tak and Gerdes, {Maarten L.} and Roberta Menafra and Ellen Duijster and Kielbasa, {Szymon M.} and Kormelink, {Tom Groot} and Stam, {Koen A.} and {van Hengel}, {Oscar R. J.} and {de Jong}, {Nicolette W.} and Hendriks, {Rudi W.} and Kloet, {Susan L.} and Maria Yazdanbakhsh and {de Jong}, {Esther C.} and {Gerth van Wijk}, Roy and Smits, {Hermelijn H.}",
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: {\textcopyright} 2023 Voskamp et al.",
year = "2023",
month = sep,
day = "4",
doi = "https://doi.org/10.1084/jem.20221111",
language = "English",
volume = "220",
journal = "Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "9",
}