IRF4 Transcription Factor-Dependent CD11b+ Dendritic Cells in Human and Mouse Control Mucosal IL-17 Cytokine Responses

By A. Schlitzer, N. McGovern, P. Teo, Teresa Zelante, K. Atarashi, Donovan Low, A. Ho, Peter See, A. Shin, Pavandip S. Wasan and 19 more. Immunity, 2013

816 citations recorded by the source corpus.

Summary Mouse and human dendritic cells (DCs) are composed of functionally specialized subsets, but precise interspecies correlation is currently incomplete. Here, we showed that murine lung and gut lamina propria CD11b+ DC populations were comprised of two subsets: FLT3- and IRF4-dependent CD24+CD64− DCs and contaminating CSF-1R-dependent CD24−CD64+ macrophages. Functionally, loss of CD24+CD11b+ DCs abrogated CD4+ T cell-mediated interleukin-17 (IL-17) production in steady state and after Aspergillus fumigatus challenge. Human CD1c+ DCs, the equivalent of murine CD24+CD11b+ DCs, also expressed IRF4, secreted IL-23, and promoted T helper 17 cell responses. Our data revealed heterogeneity in the mouse CD11b+ DC compartment and identifed mucosal tissues IRF4-expressing DCs specialized in instructing IL-17 responses in both mouse and human. The demonstration of mouse and human DC subsets specialized in driving IL-17 responses highlights the conservation of key immune functions across species and will facilitate the translation of mouse in vivo findings to advance DC-based clinical therapies.

Subfields: Immunology

View Paper: https://www.semanticscholar.org/paper/243dfa9420bf5c6aa9bf2691cc57e66ec6d13653

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In Immunology

Citations in the corpus

Two distinct interstitial macrophage populations coexist across tissues in specific subtissular niches (2019, background): “A previous study identified the high gene expression of the solute carrier organic anion transporter family member 2B1 (Slco2b1) in lung macrophages (20).”
High‐Dimensional Single‐Cell Mapping of Central Nervous System Immune Cells Reveals Distinct Myeloid Subsets in Health, Aging, and Disease (2018, neutral): “The apparent heterogeneity of cDC2s has also been noted at other organs such as the lung (Schlitzer et al., 2013) and heart (Clemente-Casares et al.”
Dendritic-cell-based therapeutic cancer vaccines. (2013, background): “Both CD1c+ and CD141+ DCs can produce IL-12, thereby enabling the generation of interferon-g (IFN-g)-secreting type 1 CD4+ T (Th1) cells and the priming of naive CD8+ T cells (Meixlsperger et al., 2013; Schlitzer et al., 2013).”
Unsupervised High-Dimensional Analysis Aligns Dendritic Cells across Tissues and Species (2016, methodology): “CD64 is highly expressed on Macs and can be used in combination with F4/80 to discriminate these cells from cDC2s (Bain et al., 2012; Gautier et al., 2012; Langlet et al., 2012; Plantinga et al., 2013; Schlitzer et al., 2013; Scott et al., 2015; Tamoutoun- Figure 1.”
Homeostatic immunity and the microbiota (2017, neutral): “While in the gut Th17 have been proposed to depend upon DC co-expressing CD11b and CD103 (dependent on Notch2 and IRF4) (Lewis et al., 2011; Persson et al., 2013; Schlitzer et al., 2013), induction of SFB specific Th17 cells depends on gut resident CX3CR1 expressing cells (Panea et al.”