Single cell RNA sequencing reveals distinct clusters of Irf8-expressing pulmonary conventional dendritic cells Article Swipe
YOU?
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· 2023
· Open Access
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· DOI: https://doi.org/10.3389/fimmu.2023.1127485
· OA: W4378745708
A single population of interferon-regulatory factor 8 (Irf8)-dependent conventional dendritic cell (cDC type1) is considered to be responsible for both immunogenic and tolerogenic responses depending on the surrounding cytokine milieu . Here, we challenge this concept of an omnipotent single Irf8-dependent cDC1 cluster through analysis of pulmonary cDCs at single cell resolution. We report existence of a pulmonary cDC1 cluster lacking Xcr1 with an immunogenic signature that clearly differs from the Xcr1 positive cDC1 cluster. The Irf8 + Batf3 + Xcr1 - cluster expresses high levels of pro-inflammatory genes associated with antigen presentation, migration and co-stimulation such as Ccr7 , Cd74 , MHC-II , Ccl5 , Il12b and Relb while, the Xcr1 + cDC1 cluster expresses genes corresponding to immune tolerance mechanisms like Clec9a , Pbx1 , Cadm1 , Btla and Clec12a . In concordance with their pro-inflammatory gene expression profile, the ratio of Xcr1 - cDC1s but not Xcr1 + cDC1 is increased in the lungs of allergen-treated mice compared to the control group, in which both cDC1 clusters are present in comparable ratios. The existence of two distinct Xcr1 + and Xcr1 - cDC1 clusters is furthermore supported by velocity analysis showing markedly different temporal patterns of Xcr1 - and Xcr1 + cDC1s. In summary, we present evidence for the existence of two different cDC1 clusters with distinct immunogenic profiles in vivo . Our findings have important implications for DC-targeting immunomodulatory therapies.
