Tongue immune compartment analysis reveals spatial macrophage heterogeneity

Ekaterini Maria Lyras, Karin Zimmermann, Lisa Katharina Wagner, Dorothea Dörr, Christoph S.N. Klose, Cornelius Fischer, Steffen Jung, Simon Yona, Avi Hai Hovav, Werner Stenzel, Steffen Dommerich, Thomas Conrad, Achim Leutz, Alexander Mildner*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


The tongue is a unique muscular organ situated in the oral cavity where it is involved in taste sensation, mastication, and articulation. As a barrier organ, which is constantly exposed to environmental pathogens, the tongue is expected to host an immune cell network ensuring local immune defence. However, the composition and the transcriptional landscape of the tongue immune system are currently not completely defined. Here, we characterised the tissue-resident immune compartment of the murine tongue during development, health and disease, combining single-cell RNA-sequencing with in situ immunophenotyping. We identified distinct local immune cell populations and described two specific subsets of tongue-resident macrophages occupying discrete anatomical niches. Cx3cr1+ macrophages were located specifically in the highly innervated lamina propria beneath the tongue epidermis and at times in close proximity to fungiform papillae. Folr2+ macrophages were detected in deeper muscular tissue. In silico analysis indicated that the two macrophage subsets originate from a common proliferative precursor during early postnatal development and responded differently to systemic LPS in vivo. Our description of the under-investigated tongue immune system sets a starting point to facilitate research on tongue immune-physiology and pathology including cancer and taste disorders.

Original languageAmerican English
Article numbere77490
StatePublished - Jun 2022

Bibliographical note

Funding Information:
We would like to thank Victoria Malchin, Jermaine Voß and Sarah Jaksch for excellent technical support, as well as the MDC animal facility, especially Juliette Bergemann, the MDC FACS core unit, particular Dr. Hans-Peter Rahn, and the MDC genomic core facility, especially Caroline Braeuning. We thank Dr. Anca Margineanu, Dr. Sandra Cristina Carneiro Raimundo and the Advanced Light Microscopy Technology Platform of the MDC for the general and technical support. C.S.N.K. was supported by grants from the German Research Foundation (FOR2599 project 5 - KL 2963/5-2; KL 2963/2-1 and KL 2963/3-1) and the European Research Council Starting Grant (ERCEA; 803087). A.M received a Heisenberg fellowship from the DFG (MI1328/3-1).

Publisher Copyright:
© 2022, eLife Sciences Publications Ltd. All rights reserved.


  • cell biology
  • cell development
  • immunology
  • inflammation
  • macrophages
  • mouse
  • single cell sequencing
  • Tongue
  • Mouse


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