Wahren-Herlenius Group
Marie Wahren-Herlenius leads the Wahren-Herlenius Group. Marie did part of her PhD training and a postdoctoral period at the Broegelmann Research Laboratory. She was appointed professor II, University of Bergen in 2020. She is also a professor at Karolinska Institutet, Stockholm, Sweden, and Department Head, Department of Medicine, Karolinska Institutet.
Main content
The majority of autoimmune diseases are more common in women than in men, but the molecular basis for this sex-bias remains poorly understood. Marie’s projects focus on the autoimmune exocrinopathy Sjögren's syndrome which has among the highest observed female-to-male ratios, to dissect the genetic and hormonal contribution to sex-dependent immune regulation at single cell resolution and how these differences may lead to autoimmune disease.
Women are at much higher risk of developing autoimmune disease, with the most extreme numbers in systemic disorders such as SLE and Sjögren’s syndrome for which more than nine out of ten patients are women. There is a clear genetic contribution to these diseases and genome-wide studies have identified polymorphisms associated with Sjögren’s syndrome. Interestingly, many of the associated genetic variants lead to differential gene regulation. However, the influence of sex, or why these immune-pathways and related genes would become dysregulated specifically in women is not clear.
In their projects, they build on the observation that genetic polymorphisms associated with Sjögren's syndrome that we identify dramatically increase the likelihood for the disease to develop in women carrying these genetic traits compared to men. Consequently, the context “female sex” may lead to a different functional impact of the genetic polymorphisms associated with systemic autoimmunity than the context “male sex”. Their projects aim to identify sex-influenced eQTLs, and dissect the genetic and hormonal contribution to sex-dependent immune regulation at single cell resolution and how these differences may lead to autoimmune disease.
More information about our research can be found here https://ki.se/en/meds/research-group-marie-wahren-herlenius
Selected publications
Sjöstrand M, Ambrosi A, Sullivan J, Malin S, Kuchroo V, Espinosa A, Wahren-Herlenius M. Expression of the immune regulator TRIM21 is controlled by interferon regulatory factors. J Immunol 2013, 191:3753-3763.
Rusakiewicz S, Nocturne G, Lazure T, Semeraro M, Flament C, Caillat-Zucman S, Sène D, Delahaye N, Vivier E, Chaba K, Poirier-Colame V, Nordmark G, Eloranta ML, Eriksson P, Theander E, Forsblad-d'Elia H, Omdal R, Wahren-Herlenius M, Jonsson R, Rönnblom L, Nititham J, Taylor KE, Lessard CJ, Sivils KL, Gottenberg JE, Criswell LA, Miceli-Richard C, Zitvogel L and Mariette X. NCR3/NKp30 Contributes to Pathogenesis in Sjogren's Syndrome. Sci Transl Med 2013, 5:195ra96.
Lessard CJ, He Li, ´Adrianto I, Ice J, Rasmussen A, Grundahl K, Kelly J, Dozmorov M, Miceli-Richard C, Bowman S, Lester S, Eriksson P, Eloranta M, Brun J, Gøransson L, Harboe E, Guthridge J, Kaufman K, Kvarnström M, Cunninghame Graham G, Grandits M, Nazmul-Hossain A, Patel K, Adler A, Maier-Moore J, Farris A, Brennan M, Lessard J, Chodosh J, Gopalakrishnan R, Hefner K, Houston G, Huang A, Hughes P, Lewis D, Radfar L, Rohrer M, Stone D, Wren J, Vyse T, Gaffney P, James J, Omdal R, Wahren-Herlenius M, Illei G, Witte T, Jonsson R, Rischmueller M, Rönnblom L, Nordmark G, Ng W for UK primary Sjögren's syndrome registry, Mariette X, Anaya J, Rhodus N, Segal B, Scofield H, Montgomery C, Harley J and Moser Sivils K. Identification of multiple genetic variants associated with Sjögren’s syndrome involved in both the innate and adaptive immune responses. Nature Genetics 2013, 45:1284-1292.
Ambrosi A and Wahren-Herlenius M. Update on the immunobiology of Sjögren’s syndrome. Curr Opin Rheumatol 2015, 27:468-75.
Brauner S, Folkersen L, Kvarnström M, Meisgen S, Petersen S, Franzén-Malmros M, Mofors J, Brokstad KA, Klareskog L, Jonsson R, Westerberg L, Trollmo C, Malmström V, Ambrosi A, Kuchroo VK, Nordmark G, Wahren-Herlenius M. H1N1 vaccination in Sjögren's syndrome triggers polyclonal B cell activation and promotes autoantibody production. Ann Rheum Dis 2017, 76:1755-1763.
Brauner S, Jiang X, Thorlacius GE, Lundberg AM, Östberg T, Yan ZQ, Kuchroo VK, Hansson GK, Wahren-Herlenius M. Augmented Th17 differentiation in Trim21 deficiency promotes a stable phenotype of atherosclerotic plaques with high collagen content. Cardiovasc Res 2018, 114:158-167.
Aqrawi LA, Mentlein L, Meneghel L, Björk A, Thorlacius GE, Ivanchenko M, Ramírez Sepúlveda JI, Skarstein K, Kvarnström M, Brauner S, Espinosa A, Wahren-Herlenius M. Clinical associations and expression pattern of the autoimmunity susceptibility factor DIORA-1 in patients with primary Sjögren's syndrome. Ann Rheum Dis 2018, 77:1840-1842.
Kyriakidis N, Kockum I, Julkunen H, Hoxha A, Salomonsson S, Meneghel L, Ebbing C, The Swedish Congenital Heart Block Study Group, Dilthey A, Eronen M, De Carolis S, Kiserud T, Ruffatti A, Kere J, Meisgen S, Wahren-Herlenius M. European families reveal MHC class I and II associations with autoimmune-mediated congenital heart block. Ann Rheum Dis 2018, 77:1381-1382.
Mofors J, Arkema EV, Björk A, Westermark L, Kvarnström M, Forsblad-d’Elia H, Magnusson Bucher S, Eriksson P, Mandl T, Nordmark G, Wahren-Herlenius M. Infections increase the risk of developing Sjögren’s syndrome. J Intern Med 2019, 285:670-680.
Mofors J, Eliasson H, Ambrosi A, Salomonsson S, Skog Andreasson A, Fored M, Ekbom A, Bergman G, Soncesson SE, Wahren-Herlenius M. Comorbidity and long-term outcome in patients with congenital heart block and their siblings exposed to Ro/SSA autoantibodies in utero. Ann Rheum Dis 2019, 78:696-703.
Björk A, Thorlacius GE, Mofors J, Richardsdotter Andersson E, Ivanchenko M, Tingström J, James T, Brokstad KA, Cox RJ, Jonsson R, Kvarnström M, Wahren-Herlenius M. Viral antigens elicit augmented immune responses in primary Sjögren's syndrome. Rheumatology (Oxford) 2020, 59:1651-1661.
Mofors J, Björk A, Smedby KE, Kvarnström, M, Forsblad-d’Elia H, Magnusson Bucher S, Eriksson P, Mandl T, Baecklund E, Nordmark G, Wahren-Herlenius M. Increased risk of multiple myeloma in primary Sjögren’s syndrome is limited to individuals with Ro/SSA and La/SSB autoantibodies. Ann Rheum Dis 2020, 79:307-308.
Sonesson SE and Wahren-Herlenius M. Surveillance of congenital heart block in highly specialised care. Lancet Rheumatology, 2020, 2:e203-204.
Sonesson SE and Wahren-Herlenius M. Mortality in congenital heart block. Lancet Rheumatology 2020, 2(10):e588-599.
Björk A, Mofors J, Wahren-Herlenius M. Environmental factors in the pathogenesis of primary Sjögren’s syndrome. J Intern Med 2020, 287:475-492.
Wahren-Herlenius M, Rönnblom L. Learning from similarities between vaccine responses and SLE. Nat Rev Rheumatol 2020, 16:355-356.
Gao Y, Liu R, He C, Basile J, Vesterlund M, Wahren-Herlenius M, Espinoza A, Hokka-Zakrisson C, Zadjali F, Yoshimura A, Karlsson M, Carow B, Rottenberg ME. SOCS3 Expression by Thymic Stromal Cells Is Required for Normal T Cell Development. Front Immunol 2021, 12:642173.
Thorlacius GE, Hultin-Rosenberg L, Sandling JK, Bianchi M, Imgenberg-Kreuz J, Pucholt P, Theander E, Kvarnström M, Forsblad-d'Elia H, Bucher SM, Norheim KB, Johnsen SJA, Hammenfors D, Skarstein K, Jonsson MV, Baecklund E, Aqrawi LA, Jensen JL, Palm Ø, Morris AP; DISSECT consortium; the ImmunoArray consortium, Meadows JRS, Rantapää-Dahlqvist S, Mandl T, Eriksson P, Lind L, Omdal R, Jonsson R, Lindblad-Toh K, Rönnblom L, Wahren-Herlenius M, Nordmark G. Genetic and clinical basis for two distinct subtypes of primary Sjögren's syndrome. Rheumatology (Oxford) 2021, 60:837-848.
Ivanchenko M, Thorlacius GE, Hedlund M, Ottosson V, Meneghel L, Björkander S, Ossoinak A, Tingström J, Bremme K, Sverremark-Ekström E, Gemzell-Danielsson K, Sonesson SE, Chemin K, Wahren-Herlenius M. Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block.
Ann Rheum Dis 2021, 80:194-202.
