Anders Lindén Group

Chronic obstructive pulmonary disease (COPD) and its pulmonary comorbidities now affect around 10% of the global population and kill more than 3 million patients each year. The cost for these disorders is estimated to exceed 3% of the total health care budget in the European union.  While the increasing exposure to tobacco smoke is the main risk factor for COPD in many countries, additional environmental exposures may account for a substantial fraction of all patients. These environmental exposures include household and air pollution resulting from the burning of biomass other than tobacco, as well as particles and dust in the traffic environment and the building industry. Events early in life, such as premature birth, pneumonia and severe asthma, also constitute risk factors. At present, under- and misdiagnosis are common problems in COPD, and the effect of the most common therapy (originally developed for asthma) is insufficient for many patients.

It is established that airway infections impair the clinical course in COPD and enhances the risk for progression of chronic airflow obstruction. This is especially true for patients who also suffer from the comorbidities chronic bronchitis and/or bronchiectasis. Unfortunately, there are no established diagnostic tools that allow us to identify individual patients at risk, and this is a logistical problem for health care. Additionally, there is no specific treatment that counteracts the susceptibility to infections in COPD. These problems relate to the poor understanding of fundamental disease mechanisms at the cellular and molecular level.

The fact that there is an increased susceptibility to infections in COPD and its comorbidities despite the local accumulation of adaptive and innate effector cells in the airways represents a paradox. From an immunological point-of-view, this paradox is poorly understood, especially in relation to the pulmonary comorbidities in COPD.  Our line of research is based on the idea that harmful exposure causes detrimental alterations in the immune signaling controlling the accumulation of anti-microbial immune cells in the airways. We think that this impairs the patient’s ability to cope with microbial stimuli. To address these matters, we characterize airway and the relevant immune signaling via cytokines in pulmonary host defence and relate it to harmful exposure. We investigate this immune signaling by comparing conditions in patients with COPD and comorbidities to those of healthy controls, but also in model studies. We map airway microbiota and its relation to cellular and molecular mechanisms in relevant body fluids, in tissue, and in primary and genetically modified cells from humans. By combining these studies, we strive to identify new cellular and molecular targets for diagnosis, monitoring and therapy of COPD and its comorbidities, ultimately for prevention as well.

Anders Lindén, professor/senior physician, anders.linden@ki.se

Elga Bernardo Bandeira de Melo, research specialist, elga.bernardo.bandeira.de.melo@ki.se

Samuel Etienne, affiliated to research, samuel.etienne@ki.se

Nikolaos Pournaras, PhD student, nikolaos.pournaras@ki.se

Patricia Ramos Ramirez, research specialist, patricia.ramos.ramirez@ki.se

Nasal production of IL-26 involving T cells in smokers with and without COPD.

Arebro J; Pournaras N; Ramos-Ramirez P; Cardenas EI; Bandeira E; Che KF; Brundin B; Bossios A; Karimi R; Nyrén S; Stjärne P; Sköld CM; Lindén A.

Article: RESPIRATORY RESEARCH 2024; 25(1): 163

Systemic IL-26 correlates with improved asthma control in children sensitized to dog allergen.

Kovach M; Käck U; Che KF; Brundin B; Konradsen J; Lindén A. Respiratory Research 2024; 25(1): 163

Article: FRONTIERS IN IMMUNOLOGY 2024; 15:1434186

Systemic increase in IL-26 is associated with severe COVID-19 and comorbid obstructive lung disease.

Cardenas E; Robertson J; Misaghian S; Brown J; Wang M; Stengelin M; Sigal G; Wohlstadter J; Gisslén M; Lindén A.

Article: FRONTIERS IN IMMUNOLOGY. 2023;14:1178135

TLR4-mediated release of heparin-binding protein in human airways: a co-stimulatory role for IL-26

Paulsson M; Cardenas EI; Che KF; Brundin B; Smith M; Qvarfordt I; Linden A

Article: AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. 2021;64(2):173-182

IL-36 Cytokines Promote Inflammation in the Lungs of Long-Term Smokers

Kovach MA; Che K; Brundin B; Andersson A; Asgeirsdottir H; Padra M; Linden SK; Qvarfordt I; Newstead MW; Standiford TJ; Linden A

Article: FRONTIERS IN IMMUNOLOGY. 2021;12:761317

Complex Involvement of Interleukin-26 in Bacterial Lung Infection

Che KF; Paulsson M; Piersiala K; Sax J; Mboob I; Rahman M; Rekha RS; Safholm J; Adner M; Bergman P; Cardell L-O; Riesbeck K; Linden A

Article: JOURNAL OF INNATE IMMUNITY. 2020;12(6):480-489

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD

Stockfelt M; Christenson K; Andersson A; Bjorkman L; Padra M; Brundin B; Ganguly K; Asgeirsdottir H; Linden S; Qvarfordt I; Bylund J; Linden A

Article: FRONTIERS IN PHARMACOLOGY. 2019;10:956

Pharmacological Modulation of Endotoxin-Induced Release of IL-26 in Human Primary Lung Fibroblasts

Che KF; Sun J; Linden A

Article: JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOY. 2019; 144(4): 1134-36.

Enhanced local production of interleukin-26 in uncontrolled compared with controlled adult asthma.

TufvessonE; Jogdand P; CheKF; Levänen B; Erjefält J; Bjermer L; Lindén A.

Article: CLINICAL SCIENCE. 2018;132(9):959-983

The neutrophil-mobilizing cytokine interleukin-26 in the airways of long-term tobacco smokers

Che KF; Tufvesson E; Tengvall S; Lappi-Blanco E; Kaarteenaho R; Levanen B; Ekberg M; Brauner A; Wheelock AM; Bjermer L; Skold CM; Linden A

Article: MOLECULAR MEDICINE. 2017;23:247-257

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Che KF; Kaarteenaho R; Lappi-Blanco E; Levanen B; Sun J; Wheelock A; Palmberg L; Skold CM; Linden A

Article: AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE. 2014;190(9):1022-1031

Interleukin-26 in Antibacterial Host Defense of Human Lungs Effects on Neutrophil Mobilization

Che KF; Tengvall S; Levanen B; Silverpil E; Smith ME; Awad M; Vikstrom M; Palmberg L; Qvarfordt I; Skold M; Linden A