Institut für Molekulare Medizin | Molekulare Medizin » Arbeitsgruppen

Research in our laboratory is focused on the role and molecular control of myeloid antigen presenting cells (APC), in particular dendritic cells (DC), in immune-mediated inflammatory diseases (IMID). Chronic IMID are caused by loss of tolerance to self- or harmless environmental antigens. DC represent a heterogeneous family of professional APC that have the unique capacity to balance immunity and tolerance. In peripheral tissues they detect pathogens as well as microbial products and inflammatory mediators, but also sample surrounding material including self- and harmless foreign antigens. Initiation of appropriate effector and regulatory T cell responses rely on the migration of sentinel DC to regional lymph nodes where they interact with naïve antigen-specific T cells. Furthermore, similarly to the closely related macrophages, DC may also contribute to the maintenance of tissue homeostasis in health and disease. As such they are attractive targets for the design of novel vaccines to treat human IMID. To this aim, it is crucial to understand how DC (subsets) are regulated and how they induce appropriate protective and tolerogenic immune responses. The molecular pathways modulating DC function we are currently studying include IL-10, E-cadherin/ β-catenin signaling, as well as post-translational modifications by A-disintegrin-and-metalloproteinases (ADAMs) and tubulin tyrosine ligase-like (TTLL) proteins. Relevant IMID models investigated in our laboratory range from contact dermatitis and psoriasis, to allergic asthma and inflammatory bowel disease and colorectal cancer, to periodontitis.

Other Activities

Selected Publications

Langerhans cells in the skin and oral mucosa - brothers in arms? Brand A, Hovav AH, Clausen BE. Eur J Immunol. 2023; 53(7):e2149499.

Classical DC2 subsets and monocyte-derived DC: Delineating the developmental and functional relationship. Backer RA, Probst HC, Clausen BE. Eur J Immunol. 2023; 53(3):e2149548.

Exclusive Expression of MyD88 on Dendritic Cells Is Sufficient to Induce Protection against Experimental Leishmaniasis. Lopez Kostka S, Kautz-Neu K, Yogev N, Lukas D, Holzmann B, Waisman A, Clausen BE, von Stebut E. J Invest Dermatol. 2022; 142(4):1230-1233.

Posttranslational modifications by ADAM10 shape myeloid antigen-presenting cell homeostasis in the splenic marginal zone. Diener N, Fontaine JF, Klein M, Hieronymus T, Wanke F, Kurschus FC, Ludwig A, Ware C, Saftig P, Bopp T, Clausen BE, Backer RA. Proc Natl Acad Sci U S A. 2021; 118(38):e2111234118.

Revisiting Current Concepts on the Tolerogenicity of Steady-State Dendritic Cell Subsets and Their Maturation Stages. Lutz MB, Backer RA, Clausen BE. J Immunol. 2021; 206(8):1681-1689.

Impaired Kupffer Cell Self-Renewal Alters the Liver Response to Lipid Overload during Non-alcoholic Steatohepatitis. Tran S, Baba I, Poupel L, Dussaud S, Moreau M, Gélineau A, Marcelin G, Magréau-Davy E, Ouhachi M, Lesnik P, Boissonnas A, Le Goff W, Clausen BE, Yvan-Charvet L, Sennlaub F, Huby T, Gautier EL. Immunity. 2020; 53(3):627-640.e5.

Tnfaip3 expression in pulmonary conventional type 1 Langerin-expressing dendritic cells regulates T helper 2-mediated airway inflammation in mice. Vroman H, van Uden D, Bergen IM, van Hulst JAC, Lukkes M, van Loo G, Clausen BE, Boon L, Lambrecht BN, Hammad H, Hendriks RW, Kool M. Allergy. 2020; 75(10):2587-2598.

E-Cadherin is Dispensable to Maintain Langerhans Cells in the Epidermis. Brand A, Diener N, Zahner SP, Tripp C, Backer RA, Karram K, Jiang A, Mellman I, Stoitzner P, Clausen BE. J Invest Dermatol. 2020; 140(1):132-142.e3.

Langerin+CD8+ Dendritic Cells in the Splenic Marginal Zone: Not So Marginal After All. Backer RA, Diener N, Clausen BE. Front Immunol. 2019; 10:741.

IL-10 signaling prevents gluten-dependent intraepithelial CD4+ cytotoxic T lymphocyte infiltration and epithelial damage in the small intestine. Costes LMM, Lindenbergh-Kortleve DJ, van Berkel LA, Veenbergen S, Raatgeep HRC, Simons-Oosterhuis Y, van Haaften DH, Karrich JJ, Escher JC, Groeneweg M, Clausen BE, Cupedo T, Samsom JN. Mucosal Immunol. 2019; 12(2):479-490.

Antagonization of IL-17A Attenuates Skin Inflammation and Vascular Dysfunction in Mouse Models of Psoriasis. Schüler R, Brand A, Klebow S, Wild J, Veras FP, Ullmann E, Roohani S, Kolbinger F, Kossmann S, Wohn C, Daiber A, Münzel T, Wenzel P, Waisman A, Clausen BE, Karbach S. J Invest Dermatol. 2019; 139(3):638-647.

Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation. Capucha T, Koren N, Nassar M, Heyman O, Nir T, Levy M, Zilberman-Schapira G, Zelentova K, Eli-Berchoer L, Zenke M, Hieronymus T, Wilensky A, Bercovier H, Elinav E, Clausen BE, Hovav AH. J Exp Med. 2018; 215(2):481-500.

TGFβR signalling controls CD103+CD11b+ dendritic cell development in the intestine. Bain CC, Montgomery J, Scott CL, Kel JM, Girard-Madoux MJH, Martens L, Zangerle-Murray TFP, Ober-Blöbaum J, Lindenbergh-Kortleve D, Samsom JN, Henri S, Lawrence T, Saeys Y, Malissen B, Dalod M, Clausen BE, Mowat AM. Nat Commun. 2017; 8(1):620.

TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity. Lukas D, Yogev N, Kel JM, Regen T, Mufazalov IA, Tang Y, Wanke F, Reizis B, Müller W, Kurschus FC, Prinz M, Kleiter I, Clausen BE, Waisman A. Proc Natl Acad Sci U S A. 2017; 114(8):E1480-E1489.

Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation. Singh TP, Zhang HH, Borek I, Wolf P, Hedrick MN, Singh SP, Kelsall BL, Clausen BE, Farber JM. Nat Commun. 2016; 7:13581.

IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine. Girard-Madoux MJ, Ober-Blöbaum JL, Costes LM, Kel JM, Lindenbergh-Kortleve DJ, Brouwers-Haspels I, Heikema AP, Samsom JN, Clausen BE. Oncotarget. 2016; 7(22):32015-30.

Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A. Wohn C, Brand A, van Ettinger K, Brouwers-Haspels I, Waisman A, Laman JD, Clausen BE. Cell Immunol. 2016; 308:57-65.

Functional Specialization of Skin Dendritic Cell Subsets in Regulating T Cell Responses.
Clausen BE, Stoitzner P. Front Immunol. 2015; 6:534.

β-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10. Fu C, Liang X, Cui W, Ober-Blöbaum JL, Vazzana J, Shrikant PA, Lee KP, Clausen BE, Mellman I, Jiang A. Proc Natl Acad Sci U S A. 2015; 112(9):2823-8.

β-catenin mediates tumor-induced immunosuppression by inhibiting cross-priming of CD8⁺ T cells. Liang X, Fu C, Cui W, Ober-Blöbaum JL, Zahner SP, Shrikant PA, Clausen BE, Flavell RA, Mellman I, Jiang A. J Leukoc Biol. 2014; 95(1):179-90.

Langerin(neg) conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Wohn C, Ober-Blöbaum JL, Haak S, Pantelyushin S, Cheong C, Zahner SP, Onderwater S, Kant M, Weighardt H, Holzmann B, Reizis B, Becher B, Prens EP, Clausen BE. Proc Natl Acad Sci U S A. 2013; 110(26):10723-8.

Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity. Zahner SP, Kel JM, Martina CA, Brouwers-Haspels I, van Roon MA, Clausen BE. J Immunol. 2011; 187(10):5069-76.

IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. Girard-Madoux MJ, Kel JM, Reizis B, Clausen BE. J Allergy Clin Immunol. 2012; 129(1):143-50.e1-10.

Langerhans cells are negative regulators of the anti-Leishmania response. Kautz-Neu K, Noordegraaf M, Dinges S, Bennett CL, John D, Clausen BE, von Stebut E. J Exp Med. 2011; 208(5):885-91.

TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis.
Kel JM, Girard-Madoux MJ, Reizis B, Clausen BE. J Immunol. 2010; 185(6):3248-55.

Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity. Noordegraaf M, Flacher V, Stoitzner P, Clausen BE. J Invest Dermatol. 2010; 130(12):2752-9.

Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML, Clausen BE. J Cell Biol. 2005; 169(4):569-76.

Identification and expression of mouse Langerin (CD207) in dendritic cells. Takahara K, Omatsu Y, Yashima Y, Maeda Y, Tanaka S, Iyoda T, Clausen BE, Matsubara K, Letterio J, Steinman RM, Matsuda Y, Inaba K. Int Immunol. 2002; 14(5):433-44.

Conditional gene targeting in macrophages and granulocytes using LysMcre mice.
Clausen BE, Burkhardt C, Reith W, Renkawitz R, Förster I. Transgenic Res. 1999; 8(4):265-77.

Funding

Open Positions