Research group Marie Wahren-Herlenius
We study the immune system and its role in autoimmunity and cancer. The group includes three principal investigators, and the immune-related diseases we study are Sjögren's syndrome, congenital heart disease and lymphoma of the skin.
Autoimmunity and cancer
In autoimmune diseases the immune system attacks and progressively destroys our own, normal tissues. In cancer, the relationship is the reverse; the immune system is unable or prevented in various ways to attack the cancer cells. Novel cancer treatments that activate the immune system are often effective but can cause autoimmune diseases as an adverse reaction - and in chronic, autoimmune diseases there is an increased risk of cancerous transformation of immune cells. These conditions reflect how delicate the balance of the immune system is, and emphasize the importance of building knowledge to understand cellular and molecular immunoregulatory mechanisms in order to develop prevention and new treatments.
Sjögren's syndrome is an autoimmune rheumatic disease that affects secretory glands, predominantly the salivary and lacrimal glands. Muscles and joints can also be affected and many patients experience great fatigue. Some patients also develop extraglandular manifestations involving eg the skin, lungs and kidneys. As part of the autoimmune process, the patients have commonly developed specific autoantibodies. In pregnancy, these autoantibodies pass over the placenta to the fetus and can cause neonatal lupus erythematosus, which includes a congenital heart block. We investigate the pathogenesis of the autoimmune inflammatory process in patients with Sjögren's syndrome and how the fetus is affected during pregnancy in women with Sjögren-associated autoantibodies. The aim is to identify underlying causes, both genetic and environmental factors, and to understand the resulting, disease-causing immunological process. Studies are performed with patients, in experimental models and in vitro. These projects are led by Professor Marie Wahren-Herlenius.
Interferons are a family of cytokines that have a crucial role in the immune system against pathogens, but are also involved in autoimmune diseases and cancer. Interferons regulate the expression of a large number of genes, with different cellular functions. We investigate the role of interferon-regulated genes in autoimmune diseases and cancer. By isolating different immune cell populations from patients and controls followed by gene expression analyses, we obtain a cell-specific map of their expression. The function of identified interferon-regulated genes is investigated both in vitro, using techniques such as lentiviral CRISPR/Cas9 and shRNA, and in vivo using experimental models. In addition, we use genome-wide CRISPR/Cas9 libraries in cancer cells to identify genes involved in metastasis and drug response. We aim to identify interferon-regulated genes that have the potential to be targets for new drugs and that are involved in the pathogenic mechanisms of autoimmune diseases and cancer respectively. This project is led by docent Alexander Espinosa.
Cutaneous T-cell lymphoma is a rare type of lymphoma that mainly affects the skin. Most patients with cutaneous T-cell lymphoma have a low-grade disease, but for largely unknown reasons, approximately 10-15% over time develop an aggressive form with high mortality. Because the lymphoma is localized to the skin, it can be easily followed with inspection and biopsies, in which the cancer cells and the patient's anti-lymphoma immune response can be examined. A specific focus of ours are the so-called natural killer cells, natural killer cells (NK cells) and their role in the body's defense against cancerous cells. We are also investigating possible immune mechanisms and tumor characteristics that control cancer development in patients with autoimmunity, including dermatomyositis and systemic lupus erythematosus. These projects are led by docent Hanna Brauner.
The results from our studies will lead to cellular and molecular understanding of both autoimmune and cancer diseases. The goal is to use the information to develop prevention, new diagnostics and treatment for these diseases.
Genetics and epigenetics of primary Sjögren syndrome: implications for future therapies.
Thorlacius GE, Björk A, Wahren-Herlenius M
Nat Rev Rheumatol 2023 May;19(5):288-306
The bromodomain protein TRIM28 controls the balance between growth and invasiveness in melanoma.
Nyberg WA, Velasquez-Pulgarin DA, He T, Sjöstrand M, Pellé L, Covacu R, Espinosa A
EMBO Rep 2023 Jan;24(1):e54944
Genome-wide association study identifies Sjögren's risk loci with functional implications in immune and glandular cells.
Khatri B, Tessneer KL, Rasmussen A, Aghakhanian F, Reksten TR, Adler A, Alevizos I, Anaya JM, Aqrawi LA, Baecklund E, Brun JG, Bucher SM, Eloranta ML, Engelke F, Forsblad-d'Elia H, Glenn SB, Hammenfors D, Imgenberg-Kreuz J, Jensen JL, Johnsen SJA, Jonsson MV, Kvarnström M, Kelly JA, Li H, Mandl T, Martín J, Nocturne G, Norheim KB, Palm Ø, Skarstein K, Stolarczyk AM, Taylor KE, Teruel M, Theander E, Venuturupalli S, Wallace DJ, Grundahl KM, Hefner KS, Radfar L, Lewis DM, Stone DU, Kaufman CE, Brennan MT, Guthridge JM, James JA, Scofield RH, Gaffney PM, Criswell LA, Jonsson R, Eriksson P, Bowman SJ, Omdal R, Rönnblom L, Warner B, Rischmueller M, Witte T, Farris AD, Mariette X, Alarcon-Riquelme ME, , Shiboski CH, , Wahren-Herlenius M, Ng WF, , Sivils KL, Adrianto I, Nordmark G, Lessard CJ
Nat Commun 2022 Jul;13(1):4287
Auxilin is a novel susceptibility gene for congenital heart block which directly impacts fetal heart function.
Meisgen S, Hedlund M, Ambrosi A, Folkersen L, Ottosson V, Forsberg D, Thorlacius GE, Biavati L, Strandberg L, Mofors J, Ramskold D, Ruhrmann S, Meneghel L, Nyberg W, Espinosa A, Hamilton RM, Franco-Cereceda A, Hamsten A, Olsson T, Greene L, Eriksson P, Gemzell-Danielsson K, Salomonsson S, Kuchroo VK, Herlenius E, Kockum I, Sonesson SE, Wahren-Herlenius M
Ann Rheum Dis 2022 Aug;81(8):1151-1161
MHC Class I-Dependent Shaping of the NK Cell Ly49 Receptor Repertoire Takes Place Early during Maturation in the Bone Marrow.
Wickström SL, Wagner AK, Fuchs S, Elemans M, Kritikou J, Mehr R, Kärre K, Johansson MH, Brauner H
J Immunol 2022 Aug;209(4):751-759
Overall survival and registration of cutaneous T-cell lymphoma patients in Sweden: a multi-center cohort and validation study.
Nenonen J, Winther AH, Leijonhufvud E, Belfrage E, Smedby KE, Brauner H
Acta Oncol 2022 May;61(5):597-601
Natural killer cells and type II interferon in Ro/SSA and La/SSB autoantibody-exposed newborns at risk of congenital heart block.
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
Ann Rheum Dis 2021 Feb;80(2):194-202
Increased risk of multiple myeloma in primary Sjögren's syndrome is limited to individuals with Ro/SSA and La/SSB autoantibodies.
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
Ann Rheum Dis 2020 Feb;79(2):307-308
miR-31 regulates energy metabolism and is suppressed in T cells from patients with Sjögren's syndrome.
Johansson A, Nyberg WA, Sjöstrand M, Moruzzi N, Bergman P, Khademi M, Andersson M, Piehl F, Berggren PO, Covacu R, Jagodic M, Espinosa A
Eur J Immunol 2019 Feb;49(2):313-322
Clinical associations and expression pattern of the autoimmunity susceptibility factor DIORA-1 in patients with primary Sjögren's syndrome.
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
Ann Rheum Dis 2018 Dec;77(12):1840-1842