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Transcriptional divergence between cDC1s and cDC2s: an AP1–IRF composite element-dependent program

Cellular & Molecular Immunology volume 18, pages 1618–1619 (2021)Cite this article

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Conventional dendritic cells (cDCs) are categorized into two main subsets, cDC1 and cDC2, distinguished by their differential expression of cell surface markers, and the development of these two cDC subsets is dependent on interferon regulatory factor 8 (IRF8) and IRF4, respectively.1 Kim et al.2 recently reported that cDC1 can be distinguished from cDC2 based on an AP1–IRF composite element (AICE)-dependent gene program. IRF8 at a high concentration engages AICEs at enhancer regions to direct a program toward establishing the cDC1 identity. These findings provide a molecular basis to explain the distinct transcriptional signatures of cDC1s and cDC2s.

Given the dependency of IRF8 and IRF4 on the development and function of cDC subsets, Kim et al. compared their individual capacities to promote cDC1 development. After retroviral-mediated expression in mouse Irf4–/–Irf8–/– bone marrow progenitors, neither Irf4 nor Irf8 restored the proportion of the cDC1 population to that found in wild-type mice, although Irf8 was slightly more efficient at recovering than Irf4.2 These results provide an energetic rationale for the cDC1-specific requirement for BATF3. Indeed, in the context of BATF3 expression, high amounts of IRF4 and IRF8 can restore the development and cross-presentation function of cDC1s. Next, studies confirmed that IRF4 and IRF8 induced similar transcriptional programs when expressed in similar amounts in cDCs; most of the transcriptional differences observed between cDC1s and cDC2s were explainable by the amount, but not the type, of the IRF protein being expressed. For instance, the expression of cDC1-specific gene Itgae, encoding CD103, was restored in the presence of high IRF4 or IRF8 levels but not low IRF conditions.2 Altogether, these results demonstrate that IRF4 and IRF8 have an equivalent cDC transcriptional impact, showing that high IRF levels are required for the initiation of an AICE-dependent transcriptional program to promote the development and function of cDC1s.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China [grant number 81870152] and the Scientific and Technological Developing Plan of Jilin Province [grant number 20200201588JC].

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Authors and Affiliations

  1. Key Laboratory of Organ Regeneration & Transplantation of the Ministry of Education, The First Hospital of Jilin University, Changchun, 130061, PR China

    Shan Zhu & Jingtao Chen

  2. Department of Cancer Center, The First Hospital of Jilin University, Changchun, 130021, PR China

    Chao Niu & Jingtao Chen

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  1. Shan Zhu
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  2. Chao Niu
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Correspondence to Jingtao Chen.

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Zhu, S., Niu, C. & Chen, J. Transcriptional divergence between cDC1s and cDC2s: an AP1–IRF composite element-dependent program. Cell Mol Immunol 18, 1618–1619 (2021). https://doi.org/10.1038/s41423-020-00628-x

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