Dermal IRF4+ dendritic cells and monocytes license CD4+ T helper cells to distinct cytokine profiles

• Published in: Nature communications Vol. 11; no. 1; p. 5637
• Main Authors: Hilligan, Kerry L., Tang, Shiau-Choot, Hyde, Evelyn J., Roussel, Elsa, Mayer, Johannes U., Yang, Jianping, Wakelin, Kirsty A., Schmidt, Alfonso J., Connor, Lisa M., Sher, Alan, MacDonald, Andrew S., Ronchese, Franca
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 06.11.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/21; 13/31; 631/250/1619/554/1898; 631/250/21/1293; 631/250/2499; 631/250/2504/133; 64/110; 64/60; Animals; Antigen-presenting cells; Antigen-Presenting Cells - immunology; Antigens; CD4 antigen; Cell Differentiation; Cell migration; Chemokines; Cytokines; Dendritic cells; Dendritic Cells - immunology; Dendritic structure; Depletion; Differentiation (biology); Female; Fungi; Helper cells; Humanities and Social Sciences; Inoculation; Interferon regulatory factor 4; Interferon Regulatory Factors - genetics; Interferon Regulatory Factors - immunology; Interferon-gamma - genetics; Interferon-gamma - immunology; Interleukin 12; Interleukin 4; Interleukin-17 - genetics; Interleukin-17 - immunology; Interleukin-4 - genetics; Interleukin-4 - immunology; Lymph nodes; Lymphocyte Activation; Lymphocytes T; Male; Mice; Mice, Inbred C57BL; Monocytes; Monocytes - cytology; Monocytes - immunology; multidisciplinary; Pathogens; Science; Science (multidisciplinary); Skin; Skin - immunology; T-Lymphocytes, Helper-Inducer - cytology; T-Lymphocytes, Helper-Inducer - immunology; Transcription; γ-Interferon
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-19463-9

Antigen (Ag)-presenting cells (APC) instruct CD4+ helper T (Th) cell responses, but it is unclear whether different APC subsets contribute uniquely in determining Th differentiation in pathogen-specific settings. Here, we use skin-relevant, fluorescently-labeled bacterial, helminth or fungal pathogens to track and characterize the APC populations that drive Th responses in vivo. All pathogens are taken up by a population of IRF4+ dermal migratory dendritic cells (migDC2) that similarly upregulate surface co-stimulatory molecules but express pathogen-specific cytokine and chemokine transcripts. Depletion of migDC2 reduces the amount of Ag in lymph node and the development of IFNγ, IL-4 and IL-17A responses without gain of other cytokine responses. Ag+ monocytes are an essential source of IL-12 for both innate and adaptive IFNγ production, and inhibit follicular Th cell development. Our results thus suggest that Th cell differentiation does not require specialized APC subsets, but is driven by inducible and pathogen-specific transcriptional programs in Ag+ migDC2 and monocytes. Antigen presenting cells induce CD4+ T helper (Th) differentiation upon pathogen encounters. Here the authors use fluorescently-labeled bacteria, helminth and fungi to track and describe the functions of IRF4+ migratory type 2 dendritic cells and monocytes in the specific induction of Th1, Th2 or Th17 responses following skin inoculation.