Funktionelle Spezialisierung von pro-inflammatorischen dendritischen Zellen bei der Psoriasis

• Antragsteller: Professor Dr. Knut Schäkel
• Fachliche Zuordnung: Dermatologie
• Förderung: Förderung von 2016 bis 2020
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 289757521

• Erstellungsjahr: 2020

Zusammenfassung der Projektergebnisse

Many studies have contributed to the current understanding of slanMo as cells with a pronounced potential to stimulate innate and adaptive immune responses. During this funding period we obtained important new findings on how in psoriasis local factors derived from fibroblasts can regulate slanMo function and how these cells are functionally modulated by medical interventions. In addition, we learned about the role of slanMo supporting inflammation in atopic dermatitis. We also performed and succeeded in establishing a cell specific and skin selective in vivo leukocyte targeting and depletion strategy having a high therapeutic potential in dermatology. Overall, there is a high interest in gaining a better understanding of the pathogenesis of skin diseases paving the way for the development of novel treatment strategies. With our studies on slanMo in the context of other mononuclear phagocytes and slan-negative nonclassical monocytes we aim for identifying the functional specialization of these cells. These studies have a high potential for unraveling the immunopathology of psoriasis and to name attractive targets for therapeutic intervention.

Projektbezogene Publikationen (Auswahl)

• ADAM17 and TIMP3 are psoriasis-relevant checkpoints controlling T helper 17 programming by inflammatory dermal dendritic cells. British Journal of Dermatology (2017)177,e239
  Kunze A, Rendon A, Oehrl S, Murphy G, Enk A, Schäkel K
  
• Autocrine TNF-α and IL-1ß prime 6-sulfo LacNAc+ dendritic cells for high level production of IL-23. Exp Dermatol. 2017 Apr; 26(4):314-316
  Kunze A, Förster U, Oehrl S, Schmitz M, Schäkel K
  
• Controlling the proinflammatory function of 6-sulfo LacNAc (slan) dendritic cells with dimethylfumarate. J Dermatol Sci. 2017 Sep;87(3):278-284
  Oehrl S, Olaru F, Kunze A, Maas M, Pezer S, Schmitz M, Schäkel K
  
• The phosphodiesterase 4 inhibitor apremilast inhibits Th1 but promotes Th17 responses induced by 6-sulfo LacNAc (slan) dendritic cells. J Dermatol Sci, 2017 Aug;87(2):110-115
  Oehrl S, Prakash H, Ebling A, Trenkler N, Wölbing P, Kunze A, Döbel T, Schmitz M, Enk A, Schäkel K
  
• Intracapillary immune complexes recruit and activate slan-expressing CD16+ monocytes in human lupus nephritis. JCI Insight. 2018 Jun 7;3(11)
  Olaru F, Döbel T, Lonsdorf AS, Oehrl S, Maas M, Enk AH, Schmitz M, Gröne EF, Gröne HJ, Schäkel K
  
• Phenotype, Function, and Mobilization of 6-Sulfo LacNAc-Expressing Monocytes in Atopic Dermatitis. Front Immunol. 2018 Jun 21;9:1352
  Baran W, Oehrl S, Ahmad F, Döbel T, Alt C, Buske-Kirschbaum A, Schmitz M, Schäkel K
  
• Regulation of IL-22BP in psoriasis. Sci Rep. 2018 Mar 23;8(1):5085
  Voglis S, Moos S, Kloos L, Wanke F, Zayoud M, Pelczar P, Giannou AD, Pezer S, Albers M, Luessi F, Huber S, Schäkel K, Kurschus FC
  
• Current Concepts on 6-sulfo LacNAc Expressing Monocytes (slanMo). Front Immunol. 2019 May 22;10:948
  Ahmad F, Döbel T, Schmitz M, Schäkel K
  
• Psoriasis Pathogenesis and Treatment. Int J Mol Sci. 2019 Mar 23;20(6)
  Rendon A, Schäkel K
  
• Skin-selective CD8 T cell depletion by photoimmunotherapy inhibits human cutaneous acute graft-versus-host disease. J Invest Dermatol. 2019 Dec 24
  Freund L, Oehrl S, Gräbe G, Gholam P, Plum T, Schäkel K