Project C7

Ionic regulation of Th17-mediated immune responses to Candida infection

Project C7 will expand the immunological expertise in research area C with a focus on T-cell immunology. The PIs of this project have previously shown that ionic signals, such as Na+ and Ca2+ gradients, are critical for the differentiation and function of murine and human Th17 cells. C7N will now investigate how ionic signals shape anti-fungal immune responses in local and systemic C. albicans infection models in mice and humans. C7 focusses in particular on Th17-cell-mediated immune responses and will identify transcriptional and metabolic factors downstream of ionic signaling as potential molecular target to augment anti-fungal immune responses in vivo.

Principal Investigators
Publications
Author Year Title Journal Links
May L, Chu CF, Zielinski CE 2024 Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients.   Cells 6;13(4):300 PubMed
Chao YY, Puhach A, Frieser D, Arunkumar M, Lehner L, Seeholzer T, Garcia-Lopez A, van der Wal M, Fibi-Smetana S, Dietschmann A, Sommermann T, Ćiković T, Taher L, Gresnigt MS, Vastert SJ, van Wijk F, Panagiotou G, Krappmann D, Groß O, Zielinski CE. 2023 Human TH17 cells engage gasdermin E pores to release IL-1α on NLRP3 inflammasome activation. Nat Immunol. 24(2):295-308 PubMed
Meiser P, Knolle MA, Hirschberger A, de Almeida GP, Bayerl F, Lacher S, Pedde AM, Flommersfeld S, Hönninger J, Stark L, Stögbauer F, Anton M, Wirth M, Wohlleber D, Steiger K, Buchholz VR, Wollenberg B, Zielinski CE, Braren R, Rueckert D, Knolle PA, Kaissis G, Böttcher JP 2023 A distinct stimulatory cDC1 subpopulation amplifies CD8+ T cell responses in tumors for protective anti-cancer immunity. Cancer Cell. 11: S1535-6108 PubMed
Wu H, Zhao X, Hochrein SM, Eckstein M, Gubert GF, Knöpper K, Mansilla AM, Öner A, Doucet-Ladevèze R, Schmitz W, Ghesquière B, Theurich S, Dudek J, Gasteiger G, Zernecke A, Kobold S, Kastenmüller W, Vaeth M 2023 Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1α-mediated glycolytic reprogramming Nat Commun. 14(1):6858 PubMed
Yin H, Karayel O, Chao YY, Seeholzer T, Hamp I, Plettenburg O, Gehring T, Zielinski C, Mann M, Krappmann D. 2022 A20 and ABIN-1 cooperate in balancing CBM complex-triggered NF-κB signaling in activated T cells. Cell Mol Life Sci. 79(2): 112 PubMed
de Almeida GP, Lichtner P, Eckstein G, Brinkschmidt T, Chu CF, Sun S, Reinhard J, Mädler SC, Kloeppel M, Verbeek M, Zielinski CE 2022 Human skin-resident host T cells can persist long term after allogeneic stem cell transplantation and maintain recirculation potential. Sci Immunol. 7(67): eabe2634 PubMed
Hochrein SM, Wu H, Eckstein M, Arrigoni L, Herman JS, Schumacher F, Gerecke C, Rosenfeldt M, Grün D, Kleuser B, Gasteiger G, Kastenmüller W, Ghesquière B, Van den Bossche J, Abel ED, Vaeth M. 2022 The glucose transporter GLUT3 controls T helper 17 cell responses through glycolytic-epigenetic reprogramming. Cell Metab 34(4):516-532 PubMed
Wu H, Brand B, Eckstein M, Hochrein SM, Shumanska M, Dudek J, Nickel A, Maack C, Bogeski I, Vaeth M 2021 Genetic Ablation of the Mitochondrial Calcium Uniporter (MCU) Does not Impair T Cell-Mediated Immunity In Vivo. Front. Pharmacol. 12: 734078 PubMed
Chu CF, Sabath F, Fibi-Smetana S, Sun S, Öllinger R, Noessner E, Chao YY, Rinke L, Winheim E, Rad R, Krug AB, Taher L, Zielinski CE 2021 Patients Without Comorbidities Display Similar Immunophenotypes Over Time Despite Divergent Disease Severities. Frontiers in Immunology 12: 601080 PubMed
Zielinski CE 2021 Regulation of T Cell Responses by Ionic Salt Signals. Cells. 10(9): 2365 PubMed
Arunkumar M, Zielinski CE 2021 T-Cell Receptor Repertoire Analysis with Computational Tools-An Immunologist’s Perspective. Cells. 10(12): 3582. PubMed
Matthias J, Heink S, Picard F, Zeiträg J, Kolz A, Chao YY, Soll D, de Almeida GP, Glasmacher E, Jacobsen ID, Riedel T, Peters A, Floess S, Huehn J, Baumjohann D, Huber M, Korn T, Zielinski CE 2020 Salt generates antiinflammatory Th17 cells but amplifies pathogenicity in proinflammatory cytokine microenvironments. J Clin Invest 130: 4587-600 PubMed