Dissecting microbial subcellular structures as targets for specific Treg-based therapies
Project Summary
CD4⁺ T cells directed against intestinal microbes or self-antigens maintain intestinal homeostasis, while dysregulated responses contribute to inflammatory bowel disease.
Regulatory T cells (Tregs) are considered central players in maintaining tolerance and have the capacity to reverse established inflammation, making them attractive targets for novel therapeutic strategies. For optimal function, Tregs must respond to the relevant antigens. In project B07, we aim to identify such target antigens within different microbial fractions and develop tools to leverage these findings for therapeutic regulation of pathological T cell responses.
Selected project-relevant publications
Roth D, Düll MM, Horst LJ, Lindemann A, Malzer X, Koop K, Zundler S, Vetter M, Jefremow A, Atreya R, Geppert C, Weidemann S, Waldner MJ, Dietrich P, Günther C, Munoz LE, Herrmann M, Scheffold A, Neurath MF, Siebler J, Schramm C, Kremer AE, Leppkes M.
Integrin αVβ6: Autoantigen and Driver of Epithelial Remodeling in Colon and Bile Ducts in Primary Sclerosing Cholangitis and Inflammatory Bowel Disease.
J Crohns Colitis. 2025 Feb 4;19(2):jjae131. doi: 10.1093/ecco-jcc/jjae131.
Saggau C, Bacher P, Esser D, Rasa M, Meise S, Mohr N, Kohlstedt N, Hutloff A, Schacht SS, Dargvainiene J, Martini GR, Stürner KH, Schröder I, Markewitz R, Hartl J, Hastermann M, Duchow A, Schindler P, Becker M, Bautista C, Gottfreund J, Walter J, Polansky JK, Yang M, Naghavian R, Wendorff M, Schuster EM, Dahl A, Petzold A, Reinhardt S, Franke A, Wieczorek M, Henschel L, Berger D, Heine G, Holtsche M, Häußler V, Peters C, Schmidt E, Fillatreau S, Busch DH, Wandinger KP, Schober K, Martin R, Paul F, Leypoldt F, Scheffold A.
Autoantigen-specific CD4+ T cells acquire an exhausted phenotype and persist in human antigen-specific autoimmune diseases.
Immunity. 2024 Oct 8;57(10):2416-2432.e8. doi: 10.1016/j.immuni.2024.08.005. Epub 2024 Sep 2. PMID: 39226901.
Martini GR, Tikhonova E, Rosati E, DeCelie MB, Sievers LK, Tran F, Lessing M, Bergfeld A, Hinz S, Nikolaus S, Kümpers J, Matysiak A, Hofmann P, Saggau C, Schneiders S, Kamps AK, Jacobs G, Lieb W, Maul J, Siegmund B, Seegers B, Hinrichsen H, Oberg HH, Wesch D, Bereswill S, Heimesaat MM, Rupp J, Kniemeyer O, Brakhage AA, Brunke S, Hube B, Aden K, Franke A, Iliev ID, Scheffold A, Schreiber S, Bacher P.
Selection of cross-reactive T cells by commensal and food-derived yeasts drives cytotoxic TH1 cell responses in Crohn’s disease.
Nat Med. 2023 Oct;29(10):2602-2614. doi: 10.1038/s41591-023-02556-5. Epub 2023 Sep 25. PMID: 37749331; PMCID: PMC10579100.
Ahlers J, Mantei A, Lozza L, Stäber M, Heinrich F, Bacher P, Hohnstein T, Menzel L, Yüz SG, Alvarez-Simon D, Bickenbach AR, Weidinger C, Mockel-Tenbrinck N, Kühl AA, Siegmund B, Maul J, Neumann C, Scheffold A.
A Notch/STAT3-driven Blimp-1/c-Maf-dependent molecular switch induces IL-10 expression in human CD4+ T cells and is defective in Crohn´s disease patients.
Mucosal Immunol. 2022 Mar;15(3):480-490. doi: 10.1038/s41385-022-00487-x. Epub 2022 Feb 15. PMID: 35169232; PMCID: PMC9038525.