IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-52942-x.html
   My bibliography  Save this article

Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming

Author

Listed:
  • Dinesh K. Deochand

    (David Z. Rosensweig Genomics Center
    Weill Cornell Medicine)

  • Marija Dacic

    (David Z. Rosensweig Genomics Center
    Weill Cornell Graduate School of Medical Sciences)

  • Michael J. Bale

    (Weill Cornell Medicine
    Weill Cornell Graduate School of Medical Sciences)

  • Andrew W. Daman

    (Weill Cornell Medicine
    Weill Cornell Graduate School of Medical Sciences)

  • Vidyanath Chaudhary

    (David Z. Rosensweig Genomics Center
    Weill Cornell Medicine)

  • Steven Z. Josefowicz

    (Weill Cornell Medicine
    Weill Cornell Graduate School of Medical Sciences)

  • David Oliver

    (David Z. Rosensweig Genomics Center)

  • Yurii Chinenov

    (David Z. Rosensweig Genomics Center)

  • Inez Rogatsky

    (David Z. Rosensweig Genomics Center
    Weill Cornell Medicine
    Weill Cornell Graduate School of Medical Sciences)

Abstract

Macrophages adopt distinct phenotypes in response to environmental cues, with type-2 cytokine interleukin-4 promoting a tissue-repair homeostatic state (M2IL4). Glucocorticoids (GC), widely used anti-inflammatory therapeutics, reportedly impart a similar phenotype (M2GC), but how such disparate pathways may functionally converge is unknown. We show using integrative functional genomics that M2IL4 and M2GC transcriptomes share a striking overlap mirrored by a shift in chromatin landscape in both common and signal-specific gene subsets. This core homeostatic program is enacted by transcriptional effectors KLF4 and the glucocorticoid receptor, whose genome-wide occupancy and actions are integrated in a stimulus-specific manner by the nuclear receptor cofactor GRIP1. Indeed, many of the M2IL4:M2GC-shared transcriptomic changes were GRIP1-dependent. Consistently, GRIP1 loss attenuated phagocytic activity of both populations in vitro and macrophage tissue-repair properties in the murine colitis model in vivo. These findings provide a mechanistic framework for homeostatic macrophage programming by distinct signals, to better inform anti-inflammatory drug design.

Suggested Citation

  • Dinesh K. Deochand & Marija Dacic & Michael J. Bale & Andrew W. Daman & Vidyanath Chaudhary & Steven Z. Josefowicz & David Oliver & Yurii Chinenov & Inez Rogatsky, 2024. "Mechanisms of epigenomic and functional convergence between glucocorticoid- and IL4-driven macrophage programming," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52942-x
    DOI: 10.1038/s41467-024-52942-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-52942-x
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-52942-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Andrés R. Muñoz-Rojas & Ilana Kelsey & Jenna L. Pappalardo & Meibin Chen & Kathryn Miller-Jensen, 2021. "Co-stimulation with opposing macrophage polarization cues leads to orthogonal secretion programs in individual cells," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    2. Giorgio Caratti & Ulrich Stifel & Bozhena Caratti & Ali J. M. Jamil & Kyoung-Jin Chung & Michael Kiehntopf & Markus H. Gräler & Matthias Blüher & Alexander Rauch & Jan P. Tuckermann, 2023. "Glucocorticoid activation of anti-inflammatory macrophages protects against insulin resistance," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. David A. Rollins & Joubert B. Kharlyngdoh & Maddalena Coppo & Bowranigan Tharmalingam & Sanda Mimouna & Ziyi Guo & Maria A. Sacta & Miles A. Pufall & Robert P. Fisher & Xiaoyu Hu & Yurii Chinenov & In, 2017. "Glucocorticoid-induced phosphorylation by CDK9 modulates the coactivator functions of transcriptional cofactor GRIP1 in macrophages," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
    4. Li Yu & Bin Zhang & Dinesh Deochand & Maria A. Sacta & Maddalena Coppo & Yingli Shang & Ziyi Guo & Xiaomin Zeng & David A. Rollins & Bowranigan Tharmalingam & Rong Li & Yurii Chinenov & Inez Rogatsky , 2020. "Negative elongation factor complex enables macrophage inflammatory responses by controlling anti-inflammatory gene expression," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    5. Maddalena Coppo & Yurii Chinenov & Maria A. Sacta & Inez Rogatsky, 2016. "The transcriptional coregulator GRIP1 controls macrophage polarization and metabolic homeostasis," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Seina Ohe & Yuji Kubota & Kiyoshi Yamaguchi & Yusuke Takagi & Junichiro Nashimoto & Hiroko Kozuka-Hata & Masaaki Oyama & Yoichi Furukawa & Mutsuhiro Takekawa, 2022. "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    2. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    3. Chuanxin Zhong & Nanxi Li & Shengzheng Wang & Dijie Li & Zhihua Yang & Lin Du & Guangxin Huang & Haitian Li & Wing Sze Yeung & Shan He & Shuting Ma & Zhuqian Wang & Hewen Jiang & Huarui Zhang & Zhangh, 2024. "Targeting osteoblastic 11β-HSD1 to combat high-fat diet-induced bone loss and obesity," Nature Communications, Nature, vol. 15(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-52942-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.