Miljöpåverkan på immunförsvar och kronisk luftvägssjukdom – Anders Lindéns forskargrupp

Vår forskning fokuserar på immunologiska mekanismer bakom olika former av miljöpåverkan på värdförsvaret hos friska personer och patienter med kroniska sjukdomar. Särskild uppmärksamhet ägnas inflammatoriska luftvägssjukdomar hos människa.

Anders Lindén, IMM

Vad vi gör

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.

 

Publikationer

Nasal production of IL-26 involving T cells in smokers with and without COPD.
Arebro J, Pournaras N, Ramos-Ramírez P, Cardenas EI, Bandeira E, Che KF, Brundin B, Bossios A, Karimi R, Nyrén S, Stjärne P, Sköld M, Lindén A
J Allergy Clin Immunol 2025 Mar;():

Systemic IL-26 correlates with improved asthma control in children sensitized to dog allergen.
Kovach MA, Käck U, Che KF, Brundin B, Konradsen JR, Lindén A
Respir Res 2024 Apr;25(1):163

Systemic increase in IL-26 is associated with severe COVID-19 and comorbid obstructive lung disease.
Cardenas EI, Robertson J, Misaghian S, Brown J, Wang M, Stengelin M, Sigal G, Wohlstadter J, Gisslén M, Lindén A
Front Immunol 2024 ;15():1434186

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, Lindén A
Front Immunol 2023 ;14():1178135

IL-36 Cytokines Promote Inflammation in the Lungs of Long-Term Smokers.
Kovach MA, Che K, Brundin B, Andersson A, Asgeirsdottir H, Padra M, Lindén SK, Qvarfordt I, Newstead MW, Standiford TJ, Lindén A
Am J Respir Cell Mol Biol 2021 Feb;64(2):173-182

Complex Involvement of Interleukin-26 in Bacterial Lung Infection.
Che KF, Paulsson M, Piersiala K, Sax J, Mboob I, Rahman M, Rekha RS, Säfholm J, Adner M, Bergman P, Cardell LO, Riesbeck K, Lindén A
Front Immunol 2021 ;12():761317

Increased CD11b and Decreased CD62L in Blood and Airway Neutrophils from Long-Term Smokers with and without COPD.
Stockfelt M, Christenson K, Andersson A, Björkman L, Padra M, Brundin B, Ganguly K, Asgeirsdottir H, Lindén S, Qvarfordt I, Bylund J, Lindén A
J Innate Immun 2020 ;12(6):480-489

Pharmacological Modulation of Endotoxin-Induced Release of IL-26 in Human Primary Lung Fibroblasts.
Che KF, Sun J, Linden A
Front Pharmacol 2019 ;10():956

Enhanced local production of IL-26 in uncontrolled compared with controlled adult asthma.
Tufvesson E, Jogdand P, Che KF, Levänen B, Erjefält JS, Bjermer L, Lindén A
J Allergy Clin Immunol 2019 Oct;144(4):1134-1136.e10

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, Levänen B, Ekberg M, Brauner A, Wheelock ÅM, Bjermer L, Sköld CM, Lindén A
Clin Sci (Lond) 2018 May;132(9):959-983

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, Levänen B, Sun J, Wheelock Å, Palmberg L, Sköld CM, Lindén A
Mol Med 2017 Oct;23():247-257

Interleukin-26 in antibacterial host defense of human lungs. Effects on neutrophil mobilization.
Che KF, Tengvall S, Levänen B, Silverpil E, Smith ME, Awad M, Vikström M, Palmberg L, Qvarfordt I, Sköld M, Lindén A
Am J Respir Crit Care Med 2014 Nov;190(9):1022-31

Medarbetare och kontakt

Gruppledare

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Besöksadress

Institute of Enviromental Medicine / Institutet för miljömedicin (IMM), Nobels väg 13, Stockholm, 17177, Sweden

Postadress

IMM, Box 210, Stockholm, 17177, Sweden

Nyckelord:
Astma Cell- och molekylärbiologi Immunologi inom det medicinska området Kroniskt obstruktiv lungsjukdom Luftvägshinder Lungmedicin och allergi Visa alla
Anna Persson
2025-04-08