Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge

Voskamp, A.L.; Tak, T.; Gerdes, M.L.; Menafra, R.; Duijster, E.; Kielbasa, S.M.; Kormelink, T.G.; Stam, K.A.; Hengel, O.R.J. van; Jong, N.W. de; Hendriks, R.W.; Kloet, S.L.; Yazdanbakhsh, M.; Jong, E.C. de; Wijk, R.G. van; Smits, H.H.

doi:doi:10.1084/jem.20221111

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...Show moreInnate 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.Innate mononuclear phagocytic cells (MPS) in the nasal mucosa are the first to encounter inhaled allergens. MPS from allergic rhinitis patients showed a pro-inflammatory response during experimental allergen challenge, while clinically silent non-allergic controls displayed a tolerizing/anti-inflammatory response.Show less

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Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge