Head: Dr. rer. nat. Ulrike Steffen
Our research group is investigating new pathobiological processes that determine the course of inflammatory joint diseases such as rheumatoid arthritis. Our research focuses on the importance of autoimmunity and specific autoantibodies, as well as the interaction of bone and the immune system. We are particularly interested in the influence of specific glycosylation patterns of antibodies or tissue proteins and their corresponding receptors.
- Function of monomeric IgA in blood
Humans have 5 classes of antibodies: IgA, IgD, IgE, IgG and IgM. IgA is mostly secreted as a dimer into the mucous membranes. However, IgA is also the second most abundant antibody type in blood after IgG. In blood, IgA is present as a monomer and, in contrast to secreted IgA, is able to regulate immune cells through the specific Fc-alpha receptor. We are investigating the role of monomeric IgA in the human immune system. In particular, we investigate the different effects of the two IgA subclasses IgA1 and IgA2.
- Immune complexes as triggers for NET formation
NETs (neutrophil extracellular traps) are extracellular structures formed by neutrophil granulocytes by DNA protrusion. NETs serve as a defense against pathogenic organisms, but can also damage the surrounding tissue, e.g. by proteolysis. Especially in autoimmune diseases, immune complexes play a role as triggers of NET formation. We are investigating how effectively the different antibody classes trigger NETs and what role antibody glycosylation plays in this process.
- Influence of glycosylation on bone and inflammation
Most proteins in the body are glycosylated. Certain glycosylation patterns can be recognized by specific receptors. Siglecs (sialic acid-binding immunoglobulin-like lectin) are receptors that recognize sialic acid-containing glycosylations and usually have anti-inflammatory effects. We are investigating the influence of Siglecs on bone and on the inflammatory course of rheumatic diseases, such as rheumatoid arthritis.
- Effect of the beta-blocker metoprolol on osteoclasts and bone density
Osteoporosis is usually caused by increased activity of bone-resorbing osteoclasts. The beta-blocker metoprolol is a commonly used drug for hypertension. We found that metoprolol inhibits osteoclast formation and activity and are now investigating the mechanisms of this inhibition in order to develop new long-term treatment strategies against osteoporosis.
|Ulrike Steffen (née Harre)||Group Leader|
|Antonio Maccataio||scientific doctoral candidate|
|Vanessa Irumva||scientific doctoral candidate|
|Carolina Brümer||scientific doctoral candidate|
|Rico Zapf||scientific doctoral candidate|
DFG-FOR2886 PANDORA: Impact of IgA and IgG ACPA on the immune system and disease onset. (STE 2867/2-2)
DFG-GRK2599: Regulation of IgA effector functions by Fc sialylation
ELAN-IZKF Universitätsklinikum Erlangen
Exploring the anti-osteoporotic effects of the β-blocker metoprolol
- DFG-FOR2886 PANDORA: Role of IgA in rheumatoid Arthritis. (HA 8163/2-1)
- DFG: „Role of Siglec-9/ Siglec-E in osteoklastogenesis“ (HA 8163/1-1)
- Bayerisches Wissenschaftsministerium: “Cytokine targeting in immune-mediated inflammatory disease and the effect on pro-resolution of COVID-19”.
- ELAN-IZKF Universitätsklinikum Erlangen: “The role of Siglec-9 and Siglec-E in osteoclastogenesis.”
- Staedtler Stiftung: “Impact of Siglec-7 and Siglec-9 on joint inflammation in rheumatoid arthritis"
- Elsbeth-Bonhoff-Stiftung: „The role of interleukin-11 in age-related bone loss“
- Gimpel AK, Maccataio A, Unterweger H, Sokolova MV, Schett G, Steffen U. (2022)IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes. Front Immunol. 12:761816.
- Sokolova MV, Hagen M, Bang H, Schett G, Rech J, Steffen U; (RETRO study group) (2021) IgA anti-citrullinated protein antibodies (IgA ACPA) are associated with flares during DMARD tapering in rheumatoid arthritis. Rheumatology (Oxford). Sep 11:keab585. Online ahead of print.
- Friščić J, Böttcher M, Reinwald C, Bruns H, Wirth B, Popp SJ, Walker KI, Ackermann JA, Chen X, Turner J, Zhu H, Seyler L, Euler M, Kirchner P, Krüger R, Ekici AB, Major T, Aust O, Weidner D, Fischer A, Andes FT, Stanojevic Z, Trajkovic V, Herrmann M, Korb-Pap A, Wank I, Hess A, Winter J, Wixler V, Distler J, Steiner G, Kiener HP, Frey B, Kling L, Raza K, Frey S, Kleyer A, Bäuerle T, Hughes TR, Grüneboom A, Steffen U, Krönke G, Croft AP, Filer A, Köhl J, Klein K, Buckley CD, Schett G, Mougiakakos D, Hoffmann MH (2021). The complement system drives local inflammatory tissue priming by metabolic reprogramming of synovial fibroblasts. Immunity. 54(5):1002-1021.e10
- Andes FT, Adam S, Hahn M, Aust O, Frey S, Grueneboom A, Nitschke L, Schett G, Steffen U (2020). The human sialic acid-binding immunoglobulin-like lectin Siglec-9 and its murine homolog Siglec-E control osteoclast activity and bone resorption. Bone. 29:115665.
- Andreev D, Liu M, Weidner D, Kachler K, Faas M, Grüneboom A, Schlötzer-Schrehardt U, Muñoz LE, Steffen U, Grötsch B, Killy B, Krönke G, Luebke AM, Niemeier A, Wehrhan F, Lang R, Schett G, Bozec A (2020). Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin. J Clin Invest. 10:134214.
- Adam S, Simon N, Steffen U, Andes FT, Scholtysek C, Müller DIH, Weidner D, Andreev D, Kleyer A, Culemann S, Hahn M, Schett G, Krönke G, Frey S, Hueber AJ (2020). JAK inhibition increases bone mass in steady-state conditions and ameliorates pathological bone loss by stimulating osteoblast function. Sci Trans Med. 12(530).
- Steffen U, Koeleman CA, Sokolova MV, Bang H, Kleyer A, Rech J, Unterweger H, Schicht M, Garreis F, Hahn J, Andes FT, Hartmann F, Hahn M, Mahajan A, Paulsen F, Hoffmann M, Lochnit G, Muñoz LE, Wuhrer M, Falck D, Herrmann M, Schett G (2020). IgA subclasses have different effector functions associated with distinct glycosylation profiles. Nat Commun. 11(1):120.
- Pfeifle R, Rothe T, Ipseiz N, Scherer HU, Culemann S, Harre U, Ackermann JA, Seefried M, Kleyer A, Uderhardt S, Haugg B, Hueber AJ, Daum P, Heidkamp GF, Ge C, Böhm S, Lux A, Schuh W, Magorivska I, Nandakumar KS, Lönnblom E, Becker C, Dudziak D, Wuhrer M, Rombouts Y, Koeleman CA, Toes R, Winkler TH, Holmdahl R, Herrmann M, Blüml S, Nimmerjahn F, Schett G, Krönke G. (2017) Regulation of autoantibody activity by the IL-23-TH17 axis determines the onset of autoimmune disease. Nat Immunol. 18(1):104-113.
- Harre U, Lang SC, Pfeifle R, Rombouts Y, Frühbeißer S, Amara K, Bang H, Lux A, Koeleman CA, Baum W, Dietel K, Gröhn F, Malmström V, Klareskog L, Krönke G, Kocijan R, Nimmerjahn F, Toes RE, Herrmann M, Scherer HU, Schett G. (2015) Glycosylation of Immunoglobulin G determines osteoclast differentiation and bone loss. Nat Commun. 6:6651.
- Harre U*, Georgess D*, Bang H, Bozec A, Axmann R, Ossipova E, Jakobsson PJ, Baum W, Nimmerjahn F, Szarka E, Sarmay G, Krumbholz G, Neumann E, Toes R, Scherer HU, Catrina AI, Klareskog L, Jurdic P, Schett G. (2012) Induction of osteoclastogenesis and bone loss by human autoantibodies against citrullinated vimentin. J Clin Invest. 122(5):1791-802. *equal contribution