AG Immune Regulation

Group Leader: Dr. Carlos Plaza Sirvent

The Immune Regulation Research Group focuses on understanding the mechanisms that control the immune response. A correct function of the immune system in the organism is essential to fight against pathogens and cancer cells. Furthermore, dysregulation of the immune system may lead to autoimmune diseases. Because of their immunosuppressive capacity, we are interested in the biology of regulatory T cells. In particular, our group aims to understand cellular and molecular mechanisms that control the suppressive function and cell survival of regulatory T cells. Our work currently focuses on deciphering the role of proteins implicated in the death receptor-mediated cell death signaling in regulatory T cells. Moreover, our research is also focused on understanding the activation of cell signaling pathways involved in survival and function of regulatory T cells. Because these cells are able to abrogate the immune response, these insights will allow us to modulate their function and control the regulatory T cell population, opening new therapeutic approaches for cancer and autoimmune diseases.

Simsek A, Bessen C, Meister TL, Urlaub D, Skaletz-Rorowski A, Brockmeyer NH, Overheu O, Reinacher-Schick A, Faissner S, Watzl C, Pfaender S, Schmitz I, Potthoff A, Plaza-Sirvent C. Humoral and cellular immune responses to repeated SARS-CoV-2 infection and vaccination in an individual living with HIV. J Eur Acad Dermatol Venereol. 2023 Mar 13. doi: 10.1111/jdv.19036.

Heinen N, Marheinecke CS, Bessen C, Blazquez-Navarro A, Roch T, Stervbo U, Anft M, Plaza-Sirvent C, Busse S, Klöhn M, Schrader J, Vidal Blanco E, Urlaub D, Watzl C, Hoffmann M, Pöhlmann S, Tenbusch M, Steinmann E, Todt D, Hagenbeck C, Zimmer G, Schmidt WE, Quast DR, Babel N, Schmitz I, Pfaender S. In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant. Front Immunol. 2022 Dec 21;13:1062210. doi: 10.3389/fimmu.2022.1062210.

Bessen C, Plaza-Sirvent C, Simsek A, Bhat J, Marheinecke C, Urlaub D, Bonowitz P, Busse S, Schumann S, Blanco EV, Skaletz-Rorowski A, Brockmeyer NH, Overheu O, Reinacher-Schick A, Faissner S, Watzl C, Pfaender S, Potthoff A, Schmitz I. Impact of SARS-CoV-2 vaccination on systemic immune responses in people living with HIV. Front Immunol. 2022 Dec 2;13:1049070. doi: 10.3389/fimmu.2022.1049070.

Faissner S, Heitmann N, Rohling R, Ceylan U, Bongert M, Plaza-Sirvent C, Marheinecke C, Pedreiturria X, Ayzenberg I, Hellwig K, Schmitz I, Pfaender S, Gold R. Preserved T-cell response in anti-CD20-treated multiple sclerosis patients following SARS-CoV-2 vaccination. Ther Adv Neurol Disord. 2022 Dec 9;15:17562864221141505. doi: 10.1177/17562864221141505.

Faissner S, Heitmann N, Plaza-Sirvent C, Trendelenburg P, Ceylan U, Motte J, Bessen C, Urlaub D, Watzl C, Overheu O, Reinacher-Schick A, Hellwig K, Pfaender S, Schmitz I, Gold R. Immune response in ofatumumab treated multiple sclerosis patients after SARS-CoV-2 vaccination. Front Immunol. 2022 Aug 31;13:980526. doi: 10.3389/fimmu.2022.980526.

Kästle M, Merten C, Hartig R, Plaza-Sirvent C, Schmitz I, Bommhardt U, Schraven B, Simeoni L. Y192 within the SH2 Domain of Lck Regulates TCR Signaling Downstream of PLC-γ1 and Thymic Selection. Int J Mol Sci. 2022 Jun 30;23(13):7271. doi: 10.3390/ijms23137271.

Carriche GM, Almeida L, Stüve P, Velasquez L, Dhillon-LaBrooy A, Roy U, Lindenberg M, Stowig T, Plaza-Sirvent C, Schmitz I, Lochner M, Simon AK, Sparwasser T. Regulating T-cell differentiation through the polyamine spermidine. J Allergy Clin Immunol. 2021 Jan;147(1):335-348.e11. doi:10.1016/j.jaci.2020.04.037

Plaza-Sirvent C, Zhao B, Bronietzki AW, Pils MC, Tafrishi N, Schuster M, Strowig T, Schmitz I (2021) A Central Role for Atg5 in Microbiota-Dependent Foxp3+ RORγt+ Treg Cell Preservation to Maintain Intestinal Immune Homeostasis. Front Immunol. 12:705436. doi: 10.3389/fimmu.2021.705436

Shah A, Plaza-Sirvent C, Weinert S, Buchbinder JH, Lavrik IN, Mertens PR, Schmitz I, Lindquist JA. YB-1 Mediates TNF-Induced Pro-Survival Signaling by Regulating NF-κB Activation. Cancers (Basel). 2020 Aug 5;12(8):2188.

Bank U, Deiser K, Plaza-Sirvent C, Osbelt L, Witte A, Knop L, Labrenz R, Jänsch R, Richter F, Biswas A, Zenclussen AC, Vivier E, Romagnani C, Kühl AA, Dunay IR, Strowig T, Schmitz I, Schüler T. c-FLIP is crucial for IL-7/IL-15-dependent NKp46+ ILC development and protection from intestinal inflammation in mice. Nat Commun. 2020 Feb 26;11(1):1056. 

Schuster M*, Plaza-Sirvent C*, Visekruna A, Huehn J, Schmitz I. Generation of Foxp3+CD25- Regulatory T-Cell Precursors Requires c-Rel and IκBNS. Front Immunol. 2019 Jul 10;10:1583. * equal contribution

Luebke T, Schwarz L, Beer YY, Schumann S, Misterek M, Sander FE, Plaza-Sirvent C, Schmitz I. c-FLIP and CD95 signaling are essential for survival of renal cell carcinoma. Cell Death Dis. 2019 May 16;10(6):384.

Chaudhry MZ, Kasmapour B, Plaza-Sirvent C, Bajagic M, Casalegno Garduño R, Borkner L, Lenac Roviš T, Scrima A, Jonjic S, Schmitz I, Cicin-Sain L. UL36 Rescues Apoptosis Inhibition and In vivo Replication of a Chimeric MCMV Lacking the M36 Gene. Front Cell Infect Microbiol. 2017 Jul 14;7:312.

Schuster M, Plaza-Sirvent C, Matthies AM, Heise U, Jeron A, Bruder D, Visekruna A, Huehn J, Schmitz I. c-REL and IκBNS Govern Common and Independent Steps of Regulatory T Cell Development from Novel CD122-Expressing Pre-Precursors. J Immunol. 2017 Aug 1;199(3):920-930.

Plaza-Sirvent C, Schuster M, Neumann Y, Heise U, Pils MC, Schulze-Osthoff K, Schmitz I. c-FLIP Expression in Foxp3-Expressing Cells Is Essential for Survival of Regulatory T Cells and Prevention of Autoimmunity. Cell Rep. 2017 Jan 3;18(1):12-22.

Annemann M, Wang Z, Plaza-Sirvent C, Glauben R, Schuster M, Ewald Sander F, Mamareli P, Kühl AA, Siegmund B, Lochner M, Schmitz I. IκBNS regulates murine Th17 differentiation during gut inflammation and infection. J Immunol. 2015 Mar 15;194(6):2888-98.

Ewald F, Annemann M, Pils MC, Plaza-Sirvent C, Neff F, Erck C, Reinhold D, Schmitz I. Constitutive expression of murine c-FLIPR causes autoimmunity in aged mice. Cell Death Dis. 2014 Apr 10;5(4):e1168.

Schuster M, Glauben R, Plaza-Sirvent C, Schreiber L, Annemann M, Floess S, Kühl AA, Clayton LK, Sparwasser T, Schulze-Osthoff K, Pfeffer K, Huehn J, Siegmund B, Schmitz I. IκB(NS) protein mediates regulatory T cell development via induction of the Foxp3 transcription factor. Immunity. 2012 Dec 14;37(6):998-1008.