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Subproject 5

The role of defects in nucleic acid metabolism for the pathogenesis of cutaneous autoimmune diseases

Lupus erythematosus is a multifactorial autoimmune disease which is caused by both genetic and environmental factors such as UV-radiation. Mutations in the gene encoding the intracellular nuclease TREX1 are the cause of familial chilblain lupus and have also been described in patients with multifactorial systemic lupus erythematosus. The aim of the project is to investigate the role of Trex1 and other nucleases in the pathogenesis of cutaneous lupus erythematosus. Besides the clinical investigation of patients and the immunohistological characterisation of lesional biopsies, we will focus on the impact of UV-radiation on the induction of inflammatory responses in primary cells of lupus patients and in animal models with nuclease deficiency. 

Subproject Manager

Platzhalter Bild

Prof. Dr. med. Claudia Günther

Klinik und Poliklinik für Dermatologie
Universitätsklinikum Carl Gustav Carus


Nicole Berndt, M.Sc., Doktorandin
Tel.: 0351-458 2692

cand. med. Gerhild Richter, Doktorandin
Tel.: 0351-458 3472

Franziska Schmidt, M.Sc., Doktorandin
Tel.: 0351-458 82272

Nick Zimmermann, BTA
Tel.: 0351-458 3472

Selected Publications

Tüngler V, König N, Günther C, Engel K, Fiehn C, Smitka M, von der Hagen M, Berner R, Lee-Kirsch MA. Response to: 'JAK inhibition in STING-associated interferonopathy' by Crow et al. Ann Rheum Dis. 2016 Dec;75(12):e76. doi: 10.1136/annrheumdis-2016-210565.

Kavanagh D, McGlasson S, Jury A, Williams J, Scolding N, Bellamy C, Gunther C, Ritchie D, Gale DP, Kanwar YS, Challis R, Buist H, Overell J, Weller B, Flossmann O, Blunden M, Meyer EP, Krucker T, Evans SJ, Campbell IL, Jackson AP, Chandran S, Hunt DP. Type I interferon causes thrombotic microangiopathy by a dose-dependent toxic effect on the microvasculature. Blood. 2016 Dec 15;128(24):2824-2833.

Lee-Kirsch MA, Günther C, Roers A. Nucleic acid-mediated autoinflammation and autoimmunity-type I interferonopathies. J Mol Med (Berl). 2016 Oct;94(10):1081-1084.

König N, Fiehn C, Wolf C, Schuster M, Cura Costa E, Tüngler V, Alvarez HA, Chara O, Engel K, Goldbach-Mansky R, Günther C, Lee-Kirsch MA. Familial chilblain lupus due to a gain-of-function mutation in STING. Ann Rheum Dis. 2017 Feb;76(2):468-472.

Peschke K, Achleitner M, Frenzel K, Gerbaulet A, Ada SR, Zeller N, Lienenklaus S, Lesche M, Poulet C, Naumann R, Dahl A, Ravens U, Günther C, Müller W, Knobeloch KP, Prinz M, Roers A, Behrendt R. Loss of Trex1 in Dendritic Cells Is Sufficient To Trigger Systemic Autoimmunity. J Immunol. 2016 Sep 15;197(6):2157-66.

Wolf C, Rapp A, Berndt N, Staroske W, Schuster M, Dobrick-Mattheuer M, Kretschmer S, König N, Kurth T, Wieczorek D, Kast K, Cardoso MC, Günther C, Lee-Kirsch MA. RPA and Rad51 constitute a cell intrinsic mechanism to protect the cytosol from self DNA. Nat Commun. 2016 May 27;7:11752.

Dobrota R, Maurer B, Graf N, Jordan S, Mihai C, Kowal-Bielecka O, Allanore Y, Distler O; EUSTAR coauthors. Prediction of improvement in skin fibrosis in diffuse cutaneous systemic sclerosis: a EUSTAR analysis. Ann Rheum Dis. 2016 Oct;75(10):1743-8.

Ingegnoli F, Boracchi P, Gualtierotti R, Smith V, Cutolo M, Foeldvari I; EUSTAR co-authors. A comparison between nailfold capillaroscopy patterns in adulthood in juvenile and adult-onset systemic sclerosis: A EUSTAR exploratory study. Microvasc Res. 2015 Nov;102:19-24.

Recke A, Vidarsson G, Ludwig RJ, Freitag M, Möller S, Vonthein R, Schellenberger J, Haase O, Görg S, Nebel A, Flachsbart F, Schreiber S, Lieb W, Gläser R, Benoit S, Sárdy M, Eming R, Hertl M, Zillikens D, König IR, Schmidt E, Ibrahim S; German AIBD Genetic Study Group. Allelic and copy-number variations of FcγRs affect granulocyte function and susceptibility for autoimmune blistering diseases. J Autoimmun. 2015 Jul;61:36-44.

Hirose M, Schilf P, Benoit S, Eming R, Gläser R, Homey B, Kunz M, Nebel A, Peitsch WK, Pföhler C, Sárdy M, Schreiber S, Zillikens D, Schmidt E, Ibrahim SM; German AIBD Genetic Study Group. Polymorphisms in the mitochondrially encoded ATP synthase 8 gene are associated with susceptibility to bullous pemphigoid in the German population. Exp Dermatol. 2015 Sep;24(9):715-7.

Günther C, Kind B, Reijns MAM, Berndt N, Martinez-Bueno M, Wolf C, Tüngler V, Chara O, Lee YA, Hübner N, Bicknell L, Blum S, Krug C, Schmidt F, Kretschmer S, Koss S, Astell KR, Ramantani G, Bauerfeind A, Morris DL, Cunninghame Graham DS, Bubeck D, Leitch A, Ralston SH, Blackburn EH, Gahr M, Witte T, Vyse TJ, Melchers I, Mangold E, Nöthen MM, Aringer M, Kuhn A, Lüthke K, Unger L, Bley A, Lorenzi A, Isaacs JD, Alexopoulou D, Conrad K, Dahl A, Roers A, Alarcon-Riquelme ME, Jackson AP, Lee-Kirsch MA. Defective removal of ribonucleotides from DNA promotes systemic autoimmunity. J Clin Invest. 2015 Jan;125(1):413-24.

Günther C, Berndt N, Wolf C, Lee-Kirsch M. Familial chilblain lupus due to a novel mutation in the exonuclease 3 domain of three prime repair exonuclease 1 (TREX1). JAMA Dermatol. 2015 Apr;151(4):426-31.

Lee-Kirsch MA, Wolf C, Günther C. Aicardi-Goutières syndrome: a model disease for systemic autoimmunity. Clin Exp Immunol. 2014 Jan;175(1):17-24.

Peschke K, Friebe F, Zimmermann N, Wahlicht T, Schumann T, Achleitner M, Berndt N, Luksch H, Behrendt R, Lee-Kirsch MA, Roers A, Günther C. Deregulated Type I IFN Response in TREX1-Associated Familial Chilblain Lupus. J Invest Dermatol. 2014 May;134(5):1456-9.

Günther C, Hillebrand M, Brunk M, Lee-Kirsch MA. Systemic involvement in TREX1-associated familial chilblain lupus. J Am Acad Dermatol 2013 Oct;69(4):e179-81.

Hänsel A, Günther C, Baran W, Bidier M, Lorenz HM, Schmitz M, Bachmann M, Döbel T, Enk AH, Schäkel K. Human 6-sulfo LacNAc (slan) dendritic cells have molecular and functional features of an important pro-inflammatory cell type in lupus erythematosus. J Autoimmun 2013;40:1-8.

Aringer M, Günther C, Lee-Kirsch MA. Innate immune processes in lupus erythematosus. Clin Immunol. 2013 Jun;147(3):216-22.

Rehberger P, Müller H, Günther C, Schmitt J. Treatment satisfaction and health status in patients with systemic sclerosis. J Dtsch Dermatol Ges 2012;10(12):905-12.

Tüngler V, Silver RM, Walkenhorst H, Günther C, Lee-Kirsch MA. Inherited or de novo mutation affecting aspartate 18 of TREX1 results in either familial chilblain lupus or Aicardi-Goutières syndrome. Br J Dermatol 2012;167(1):212-4.


Günther C, Aringer M, Lochno M, Kämmerer E, Bauer A, Wozel G, Meurer M. TNF-alpha blockade with infliximab in a patient with lupus erythematosus profundus. Acta Derm Venereol 2012;92(4):401-3.

Günther C, Starke J, Zimmermann N, Schäkel K. Human 6-sulfo LacNAc (slan) dendritic cells are a major population of dermal dendritic cells in steady state and inflammation. Clin Exp Dermatol 2012;37:169-176.


Günther C, Carballido-Perrig N, Kaesler S, Carballido JM, Biedermann T. CXCL16 and CXCR6 are upregulated in psoriasis and mediate cutaneous recruitment of human CD8+ T cells. J Invest Dermatol 2012;132(3 Pt 1):626-34.

Müller H, Rehberger P, Günther C, Schmitt J. Determinants of disability, quality of life and depression in dermatologicalpatients with systemicscleroderma. Br J Dermatol 2012;166(2):343-53.

Günther C, Wozel G, Meurer M, Pfeiffer C. Up-regulation of CCL11 and CCL26 is associated with activatedeosinophils in bullous pemphigoid. Clin Exp Immunol 2011;166(2):145-53.

Hänsel A*, Günther C*, Ingwersen J, Starke J, Schmitz M, Bachmann M, Meurer M, Rieber EP, Schäkel K. Human slan (6-sulfo LacNAc) dendritic cells are inflammatory dermal dendritic cells in psoriasis and drive strong TH17/TH1 T-cell responses. J Allergy Clin Immunol 2011;127(3):787-94.e1-9. (*equal contribution)

Günther C, Zimmermann N, Berndt N, Grosser M, Stein A, Koch A, Meurer M. Up-regulation of the chemokine CCL18 by macrophages is a potential immunomodulatory pathway in cutaneous T-cell lymphoma. Am J Pathol 2011;179(3):1434-42.

Günther C, Meurer M, Stein A, Viehweg A, Lee-Kirsch MA. Familial chilblain lupus – a monogenic form of cutaneous lupus erythematosus due to a heterozygous mutation in TREX1. Dermatology 2009;219(2):162-6.


Günther C, Carballido-Perrig N, Kopp T, Carballido JM, Pfeiffer C. CCL18 is expressed in patients with bullous pemphigoid and parallels disease course. Br J Dermatol 2009;160(4):747-55.


Günther C, Laske J, Frind A, Julius U, Pfeiffer C. Successful therapy of pemphigus vulgaris with immunoadsorption using the TheraSorbTM adsorber. J Dtsch Dermatol Ges 2008;6(8):661-3.


Günther C, Hertl M, Meurer M. Diagnostic use of autoantibodies. Hautarzt 2007;58(12):1063-1075.


Günther C, Pfeiffer C. Chemokine in der Pathogenese der atopischen Dermatitis. Allergojournal 2007;03:186-192.


Novak H, Muller A, Harrer N, Günther C, Carballido JM, Woisetschlager M. CCL23 expression is induced by IL-4 in a STAT6-dependent fashion. J Immunol 2007;178(7):4335-41.


Günther C, Bello-Fernandez C, Kopp T, Kund J, Carballido-Perrig N, Hinteregger S, Fassl S., Schwärzler C, Lametschwandtner G, Stingl G, Biedermann T and Carballido JM. CCL18 is expressed in atopic dermatitis and mediates skin homing of human memory T cells. J Immunol 2005;174:1723-1728.


Lametschwandtner G, Biedermann T, Schwärzler C, Günther C, Kund J, Fassl S, Hinteregger S, Carballido-Perrig N, Szabo SJ, Glimcher LH and Carballido JM. Sustained T-bet expression confers polarized human Th2 cells with Th1-like cytokine production and migratory capacities. J Allergy Clin Immunol 2004;113(5):987-94.