T Zell Reaktivierung im akuten Nierenversagen
Zusammenfassung der Projektergebnisse
For the first time, our transcriptome analysis revealed genes specific for effector T cell reactivation besides T cell priming and differentiation. Via sorting and transcriptome analysis we observed that the amount of genes uniquely regulated in effector T cell activation is comparable to the amount defining linage differentiation and goes beyond T cell activation per se compared to naïve cell activation. We thus find that on a transcriptome level, effector reactivation is a uniquely defined event. The expression of selected genes from this transcriptome analysis showed similar tendencies in expression in all CD4 + T cell effector subpopulations, although expression strength differed. These results might indicate that reactivation could be a process sharing overlap over the effector subpopulation types. It is particularly interesting that most of the identified genes were not described or characterized in T cell populations before. Clec4e is one identified gene, which was not only significantly upregulated in vitro in all CD4+ T cell subpopulations, but was also significantly upregulated in sorted CD4+ T cells from inflamed kidneys (NTN model) and significantly upregulated in human T H1 cells upon reactivation. To our knowledge, Clec4e was mainly characterized in innate immune cells and there is no study available, which describes the expression of Clec4e on T cells. Furthermore, our results showed that Clec7a was significantly upregulated in vitro in all CD4+ T cell subpopulations, except TH17 cells - although there was a trend towards upregulation. Furthermore, it was significantly upregulated on protein level on sorted CD4 + T cells from inflamed kidneys (NTN) and on Nur77GFP+ CD4+ T cells from inflamed CNS (EAE), although it was not significantly upregulated on human TH1 cells, but results showed a trend towards upregulation. Clec7a is mainly described on innate immune cells, but a recent publication showed that Clec7a expression in CAR T cells leads to significantly higher cytokine secretion and may increase their clinical potential. This study and our findings make Clec7a a possible candidate for immunotherapy. Taken together, our study identified effector reactivation as a transcriptionally distinct process compared to effector differentiation as well as T cell activation. Furthermore, our studies reveal a variety of interesting genes defining this process, however in vivo results have varied significantly in the validation of these genes, indicating the need for further research as the in vivo microenvironment appears to significantly shape this process beyond our idealized in vitro setting.
Projektbezogene Publikationen (Auswahl)
- PRN473, an inhibitor of Bruton's tyrosine kinase, inhibits neutrophil recruitment via inhibition of macrophage antigen-1 signalling. Br J Pharmacol. 2018 Feb;175(3):429- 439
Herter JM, Margraf A, Volmering S, Correia BE, Bradshaw JM, Bisconte A, Hill RJ, Langrish CL, Lowell CA, Zarbock A
(Siehe online unter https://doi.org/10.1111/bph.14090) - Addition of Radiotherapy to Immunotherapy: Effects on Outcome of Different Subgroups Using a Propensity Score Matching. Cancers (Basel). 2020 Aug 27;12(9):2429
Trommer M, Kinsky J, Adams A, Hellmich M, Schlaak M, von Bergwelt-Baildon M, Celik E, Rosenbrock J, Morgenthaler J, Herter JM, Linde P, Mauch C, Theurich S, Marnitz S, Baues C
(Siehe online unter https://doi.org/10.3390/cancers12092429) - Radiation induced regulation of endothelial adhesion receptors. Experimental Biology (2020) - FASEB J April 2020 34:S1
Kiljan M, Weil S, Vásquez-Torres A, Hettich M, Reinscheid M, Ibruli O, Cai J, Baues C, Marnitz S, Baus W, Herter-Sprie G, Herter J
(Siehe online unter https://doi.org/10.1096/fasebj.2020.34.s1.09424) - Stereotaktisches Roboter-Bestrahlungssystem als Plattform für Kleintiermodellstudien. [Stereotactic roboterradiationsystem as a platform for small animal irradiation studies]. 51st Annual meeting of the German Society of Medicine Physics – Session 21 V90
Vásquez Torres A, Kiljan M, Hettich M, Ibruli O, Herter-Sprie GS, Herter JM
- CyberKnife radiation therapy as a platform for translational mouse studies. Int J Radiat Biol. 2021;97(9):1261-1269
Kiljan M, Weil S, Vásquez-Torres A, Hettich M, Mayer M, Ibruli O, Reinscheid M, Heßelmann I, Cai J, Niu LN, Sahbaz Y, Baues C, Baus WW, Kamp F, Marnitz S, Herter-Sprie GS, Herter JM
(Siehe online unter https://doi.org/10.1080/09553002.2021.1934749) - HSP90-Inhibition und Radiotherapie führen zur synergistischen Aktivierung des cGAS/STING Signalwegs. 27. Jahrestagung der deutschen Gesellschaft für Radioonkologie (2021) [#214, June 2021]
Hesselmann I, Reinscheid M, Kiljan M, Niu L, Cai J, Wagner E, Sahbaz Y, Mayer M, Kamp F, Baues C, Marnitz-Schulze S, Herter-Sprie GS, Herter JM
- Impact of radiation therapy on vascular endothelial adhesion receptor expression. Experimental Biology (2021) [R3429]
Wagner E, Niu L, Kiljan M, Ibruli O, Hesselmann I, Sahbaz Y, Cai J, Hettich M, Mayer M, Kamp F, Baues C, Marnitz S, Herter JM, Herter-Sprie GS
- Strahlentherapie des vaskulären Endothels führt zur Modulation von Adhäsionsrezeptoren. 27. Jahrestagung der deutschen Gesellschaft für Radioonkologie (2021) [#348, June 2021]
Wagner E, Niu L, Kiljan M, Ibruli O, Hesselmann I, Sahbaz Y, Cai J, Hettich M, Mayer M, Kamp F, Baues C, Marnitz S, Herter-Sprie GS, Herter JM
- Synergy of HSP90 Inhibition and Radiation Therapy for cGAS/STING Pathway Activation. Experimental Biology (2021) [R3404]
Hesselmann I, Reinscheid M, Kiljan M, Niu L, Cai J, Wagner E, Sahbaz Y, Mayer M, Kamp F, Baues C, Marnitz-Schulze S, Herter-Sprie GS, Herter JM
- Transcriptome analysis of reactivated T H1 cells reveal distinct differences between priming and reactivation processes. Experimental Biology (2021) [R2700]
Kiljan M, Camacho Velázquez O, Ercanoglu M, Hesselmann I, Sahbaz Y, Wagner E, Cai J, Niu L, Lackmann JW, Hillmer A, Sorokin L, Engelbertsen D, Klein F, Baues C, Marnitz-Schulze S, Herter-Sprie GS, Herter JM
(Siehe online unter https://doi.org/10.1096/fasebj.2021.35.S1.02700) - Influence of chemoradiation on the immune microenvironment of cervical cancer patients. Strahlenther Onkol. 2022 Oct 17
Herter JM, Kiljan M, Kunze S, Reinscheid M, Ibruli O, Cai J, Niu L, Heßelmann I, Trommer M, Herter- Sprie GS, Köhler C, Marnitz S
(Siehe online unter https://doi.org/10.1007/s00066-022-02007-z) - Oncologic Outcome and Immune Responses of Radiotherapy with Anti-PD-1 Treatment for Brain Metastases Regarding Timing and Benefiting Subgroups. Cancers (Basel). 2022 Feb 27;14(5):1240
Trommer M, Adams A, Celik E, Fan J, Funken D, Herter JM, Linde P, Morgenthaler J, Wegen S, Mauch C, Franklin C, Galldiks N, Werner JM, Kocher M, Rueß D, Ruge M, Meißner AK, Baues C, Marnitz S
(Siehe online unter https://doi.org/10.3390/cancers14051240)
