Redefine the Transcriptional and Epigenetic Signature of Tissue-associated Regulatory T Cells

Recently Delacher and colleagues were able to redefine the transcriptional and epigenetic signature of tissue-associated regulatory T cells (Treg) in mice and humans (Delacher et al. 2021). They could demonstrate, that Treg cells from healthy tissues share distinct expression patterns with tumor-infiltrating Treg cells. Based on these and other facts discussed in the manuscript, the authors concluded that Treg cells can undertake the task of tissue repair functions in malignant solid tumors, but also in healthy tissues. This concept was proofed by using 3D-skin reconstruction models in the context of wound healing (for details see (Groeber et al. 2015). After wounding of the reconstructed human 3D-skin models by an 2mm punch, soluble mediators of tissue-associated Treg cells were added to the assay. Non-invasive methods, such as impedance spectroscopy can be used for the documentation and quantification of wound healing. Of note, the authors used for the first time advanced imaging techniques, allowing the quantification of the in-situ findings wound healing more precisely.
The high-resolution microscope system TissueFAXS i PLUS (TissueGnostics, Vienna, Austria) was used to generated computer-based recordings of images of paraffin sections stained with hematoxylin & eosin (HE). This technology enables both i) the automated generation of images and ii) the merging of individual images into one data package, that contains the metadata for subsequent quantitative software-based analysis.
Given the fact that wound healing is associated with the new formation of the Stratum corneum including the adjacent transition zone to the Stratum granulosum (Kiesewetter et al., 2019) the authors used the StrataQuest software (TissueGnostics, Vienna, Austria) and a special imaging algorithm for subsequent analysis. The details are shown in the publication (Delacher et al. 2021, Figure 7G and Figure S7G).
In conclusion the StrataQuest software allows a precise detection, separation and quantification of tissues such as Stratum corneum and Stratum granulosum from the adjoining keratinocytes in HE-stained paraffin sections.

written by Prof. Dr. Uwe Ritter (RCI Regensburg Center of Interventional Immunology, University of Regensburg, Germany)

References and Further Reading

1. Delacher M, Simon M, Sanderink L, Hotz-Wagenblatt A, Wuttke M, Schambeck K, Schmidleithner L, Bittner S, Pant A, Ritter U, Hehlgans T, Riegel D, Schneider V, Groeber-Becker FK, Eigenberger A, Gebhard C, Strieder N, Fischer A, Rehli M, Hoffmann P, Edinger M, Strowig T, Huehn J, Schmidl C, Werner JM, Prantl L, Brors B, Imbusch CD, Feuerer M. Single-cell chromatin accessibility landscape identifies tissue repair program in human regulatory T cells. Immunity. 2021 Apr 13;54(4):702-720.e17. doi: 10.1016/j.immuni.2021.03.007. Epub 2021 Mar 30. PMID: 33789089; PMCID: PMC8050210.
2. Groeber F, Engelhardt L, Egger S, Werthmann H, Monaghan M, Walles H, Hansmann J. Impedance spectroscopy for the non-destructive evaluation of in vitro epidermal models. Pharm Res. 2015 May;32(5):1845-54. doi: 10.1007/s11095-014-1580-3. Epub 2014 Dec 3. PMID: 25467957; PMCID: PMC4381093.

3. Kiesewetter L, Littau L, Walles H, Boccaccini AR, Groeber-Becker F. Reepithelialization in focus: Non-invasive monitoring of epidermal wound healing in vitro. Biosensors & Bioelectronics. 2019 Oct;142:111555. DOI: 10.1016/j.bios.2019.111555

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