Institut für Molekulare Medizin Mainz

AG Clausen

Research

Research in our laboratory is focused on the role and molecular control of myeloid cells, 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 antigen presenting cells 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 are believed to 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, TGF-β and β-catenin signaling. Relevant IMID models investigated in our laboratory range from contact dermatitis and psoriasis, to allergic asthma and inflammatory bowel disease (IBD), to autoimmunity, e.g. experimental autoimmune encephalomyelitis (EAE) and rheumatoid arthritis.

Other Activities

Selected Publications

For a complete publication list see Pubmed

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* (2017). TGF-β inhibitor Smad7 regulates dendritic cell-induced autoimmunity. Proc Natl Acad Sci U S A. 114(8):E1480-E1489. PMID: 28167776. [*equal contribution]

Ober-Blöbaum JL, Ortner D, Haid B, Brand A, Tripp C, Clausen BE*, Stoitzner P* (2017). Monitoring Skin Dendritic Cells in Steady State and Inflammation by Immunofluorescence Microscopy and Flow Cytometry. Methods Mol Biol. 1559:37-52. PMID: 28063035. [*equal contribution]

Singh TP, Zhang HH, Borek I, Wolf P, Hedrick MN, Singh SP, Kelsall BL, Clausen BE, Farber JM (2016). Monocyte-derived inflammatory Langerhans cells and dermal dendritic cells mediate psoriasis-like inflammation. Nat Commun. 7:13581. PMID: 27982014.

Sichien D, Scott CL, Martens L, Vanderkerken M, Van Gassen S, Plantinga M, Joeris T, De Prijck S, Vanhoutte L, Vanheerswynghels M, Van Isterdael G, Toussaint W, Madeira FB, Vergote K, Agace WW, Clausen BE, Hammad H, Dalod M, Saeys Y, Lambrecht BN, Guilliams M (2016). IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively. Immunity. 45(3):626-40. PMID: 27637148.

Girard-Madoux MJ, Ober-Blöbaum JL, Costes LM, Kel JM, Lindenbergh-Kortleve DJ, Brouwers-Haspels I, Heikema AP, Samsom JN*, Clausen BE* (2016). IL-10 control of CD11c+ myeloid cells is essential to maintain immune homeostasis in the small and large intestine. Oncotarget. 7(22):32015-30. PMID: 27027442. [*equal contribution]

Wohn C, Brand A, van Ettinger K, Brouwers-Haspels I, Waisman A, Laman JD, Clausen BE (2016). Gradual development of psoriatic skin lesions by constitutive low-level expression of IL-17A. Cell Immunol. 308:57-65. PMID: 26653007.

Alves CH, Ober-Blöbaum JL, Brouwers-Haspels I, Asmawidjaja PS, Mus AM, Razawy W, Molendijk M, Clausen BE*, Lubberts E* (2015). Dendritic Cell-Specific Deletion of β-Catenin Results in Fewer Regulatory T-Cells without Exacerbating Autoimmune Collagen-Induced Arthritis. PLoS One. 10(11):e0142972. PMID: 26587585. [*equal contribution]

Clausen BE, Stoitzner P (2015). Functional Specialization of Skin Dendritic Cell Subsets in Regulating T Cell Responses. Front Immunol. 6:534. PMID: 26557117.

Croxford AL, Lanzinger M, Hartmann FJ, Schreiner B, Mair F, Pelczar P, Clausen BE, Jung S, Greter M, Becher B (2015). The Cytokine GM-CSF Drives the Inflammatory Signature of CCR2+ Monocytes and Licenses Autoimmunity. Immunity. 43(3):502-14. PMID: 26341401.

Girard-Madoux MJ, Kautz-Neu K, Lorenz B, Ober-Blöbaum JL, von Stebut E*, Clausen BE* (2015). IL-10 signaling in dendritic cells attenuates anti-Leishmania major immunity without affecting protective memory responses. J Invest Dermatol. 135(11):2890-4. PMID: 26099027. [*equal contribution]

Fu C, Liang X, Cui W, Ober-Blöbaum JL, Vazzana J, Shrikant PA, Lee KP, Clausen BE, Mellman I, Jiang A (2015). β-Catenin in dendritic cells exerts opposite functions in cross-priming and maintenance of CD8+ T cells through regulation of IL-10. Proc Natl Acad Sci U S A. 112(9):2823-8. PMID: 25730849.

Anandasabapathy N, Feder R, Mollah S, Tse SW, Longhi MP, Mehandru S, Matos I, Cheong C, Ruane D, Brane L, Teixeira A, Dobrin J, Mizenina O, Park CG, Meredith M, Clausen BE, Nussenzweig MC, Steinman RM (2014). Classical Flt3L-dependent dendritic cells control immunity to protein vaccine. J Exp Med. 211(9):1875-91. PMID: 25135299.

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 (2013). Langerin(neg) conventional dendritic cells produce IL-23 to drive psoriatic plaque formation in mice. Proc Natl Acad Sci U S A. 110(26):10723-8. PMID: 23754427.

Girard-Madoux MJ, Kel JM, Reizis B, Clausen BE (2012). IL-10 controls dendritic cell-induced T-cell reactivation in the skin to limit contact hypersensitivity. J Allergy Clin Immunol. 129(1):143-50.e1-10. PMID: 21975175.

Zahner SP, Kel JM, Martina CA, Brouwers-Haspels I, van Roon MA, Clausen BE (2011). Conditional deletion of TGF-βR1 using Langerin-Cre mice results in Langerhans cell deficiency and reduced contact hypersensitivity. J Immunol. 187(10):5069-76. PMID: 21998450.

Kautz-Neu K, Noordegraaf M, Dinges S, Bennett CL, John D, Clausen BE*, von Stebut E* (2011). Langerhans cells are negative regulators of the anti-Leishmania response. J Exp Med. 208(5):885-91. PMID: 21536741. [*equal contribution]

Kel JM, Girard-Madoux MJ, Reizis B, Clausen BE (2010). TGF-beta is required to maintain the pool of immature Langerhans cells in the epidermis. J Immunol. 185(6):3248-55. PMID: 20713882.

Noordegraaf M, Flacher V, Stoitzner P, Clausen BE (2010). Functional redundancy of Langerhans cells and Langerin+ dermal dendritic cells in contact hypersensitivity. J Invest Dermatol. 130(12):2752-9. PMID: 20703247.

Nagao K, Ginhoux F, Leitner WW, Motegi S, Bennett CL, Clausen BE, Merad M, Udey MC (2009). Murine epidermal Langerhans cells and langerin-expressing dermal dendritic cells are unrelated and exhibit distinct functions. Proc Natl Acad Sci U S A. 106(9):3312-7. PMID:19218433.

Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML, Clausen BE (2005). Inducible ablation of mouse Langerhans cells diminishes but fails to abrogate contact hypersensitivity. J Cell Biol. 169(4):569-76. PMID:15897263.

Funding

The work in our laboratory is supported by the German Research Foundation (DFG), the Fritz Thyssen Foundation and the Mainz Research Center for Immunotherapy (FZI)