November 2021 - Johanna Strobl

Dr. Johanna Strobl

MedUni Wien RESEARCHER OF THE MONTH November 2021

The skin contains a population of tissue-resident memory T cells (Trm) that contributes to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of Trm has been obtained from murine studies, little is known about the biology of human cutaneous Trm. We showed that host-derived CD69+ αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting Trm in the skin, whereas tissue retention molecules and stem cell markers were displayed by Trm. The transcription factor RUNX3 and the surface molecule Galectin-3 were preferentially expressed by host T cells on the RNA and protein levels, suggesting two novel markers for human skin Trm. Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived Trm, indication a contribution of these cells to the pathogenesis of GVHD. Together, our studies highlight the relationship between the local human skin environment and long-term persisting Trm and challenge the paradigm of one-directional T cell response in GVHD.

Selected Literature

1. Strobl J., Pandey R.V., Krausgruber T., Bayer N., Kleissl L., Reininger B., Vieyra-Garcia P., Wolf P., Jentus M.M., Mitterbauer M., Wohlfarth P., Rabitsch W., Stingl G., Bock C., Stary G. Long-term skin resident memory T cells proliferate in situ and are involved in human graft-versus-host disease. Sci Transl Med. In press, publication date: Nov 18, 2020
2. Stary V., Pandey R.V., Strobl J., Kleissl L., Starlinger P., Pereyra D., Weninger W., Fischer G.F., Bock C., Farlik M., Stary G. A discrete subset of epigenetically primed human NK cells mediates antigen-specific immune responses. Science Immunology 2020. 5: eaba6232
3. Brüggen MC*, Strobl J*, Koszik F, Naito R, Vierhapper M, Li N, Stary G, Kiprov H, French L, Stingl G. Subcutaneous White Adipose Tissue of Healthy Young Individuals Harbors a Leukocyte Compartment Distinct from Skin and Blood. J Invest Dermatol. 2019 Sep;139(9):2052-2055.e7. * authors contributed equally
4. Strobl J, Pandey RV, Krausgruber T, Kleissl L, Reininger B, Herac M, Bayer N, Krall C, Wohlfarth P, Mitterbauer M, Kalhs P, Rabitsch W, Bock C, Hopfinger G*, Stary G*. Anti-Apoptotic Molecule BCL2 Is a Therapeutic Target in Steroid-Refractory Graft-Versus-Host Disease. J Invest Dermatol. 2020 Apr 2:S0022-202X(20)31252-5.
5. Vojtech L, Woo S, Hughes S, Levy C, Ballweber L, Sauteraud RP, Strobl J, Westerberg K, Gottardo R, Tewari M, Hladik F. Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res. 2014 Jun;42(11):7290-304. Epub 2014 May 16.