ILC2 Lung-Homing in Cystic Fibrosis Patients: Functional Involvement of CCR6 and Impact on Respiratory Failure

Frontiers in Immunology
Anja Schulz-KuhntImke Atreya


Cystic fibrosis patients suffer from a progressive, often fatal lung disease, which is based on a complex interplay between chronic infections, locally accumulating immune cells and pulmonary tissue remodeling. Although group-2 innate lymphoid cells (ILC2s) act as crucial initiators of lung inflammation, our understanding of their involvement in the pathogenesis of cystic fibrosis remains incomplete. Here we report a marked decrease of circulating CCR6+ ILC2s in the blood of cystic fibrosis patients, which significantly correlated with high disease severity and advanced pulmonary failure, strongly implicating increased ILC2 homing from the peripheral blood to the chronically inflamed lung tissue in cystic fibrosis patients. On a functional level, the CCR6 ligand CCL20 was identified as potent promoter of lung-directed ILC2 migration upon inflammatory conditions in vitro and in vivo using a new humanized mouse model with light-sheet fluorescence microscopic visualization of lung-accumulated human ILC2s. In the lung, blood-derived human ILC2s were able to augment local eosinophil and neutrophil accumulation and induced a marked upregulation of pulmonary type-VI collagen expression. Studies in primary human lung fibroblasts additi...Continue Reading


Aug 1, 1991·The American Journal of Physiology·R H Goldstein
Jun 1, 1995·American Journal of Respiratory and Critical Care Medicine·U SpecksR Timpl
May 1, 1994·Thorax·D Y KollerR Urbanek
Aug 12, 1998·American Journal of Respiratory and Critical Care Medicine·I DurieuY Pacheco
Jun 8, 1999·Annual Review of Immunology·K NelmsW E Paul
Aug 11, 2000·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·C MoserN Høiby
May 16, 2003·American Journal of Respiratory Cell and Molecular Biology·Timothy D StarnerPaul B McCray
Feb 1, 2005·Alimentary Pharmacology & Therapeutics·J PulestonA Platt
Aug 23, 2006·Archives of Disease in Childhood·S Rao, J Grigg
Jul 4, 2007·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·P J DubinJ K Kolls
Dec 4, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tomohide YamazakiChen Dong
May 14, 2009·International Journal of Chronic Obstructive Pulmonary Disease·Jeroen J W LieskerWim Timens
Nov 27, 2010·The European Respiratory Journal·M BrodlieC Ward
Mar 17, 2011·Matrix Biology : Journal of the International Society for Matrix Biology·Jean-François GroulxJean-François Beaulieu
Apr 9, 2011·American Journal of Respiratory and Critical Care Medicine·Hui-Leng TanJane C Davies
Mar 10, 2012·American Journal of Respiratory Cell and Molecular Biology·Dmitry Ratner, Christian Mueller
Apr 7, 2012·Nature Medicine·Taylor Sitarik Cohen, Alice Prince
Dec 12, 2012·The Journal of Allergy and Clinical Immunology·Lucie RousselSimon Rousseau
Jan 12, 2013·American Journal of Respiratory and Critical Care Medicine·Kerstin TiringerThomas Eiwegger
Apr 23, 2013·Thorax·Hui-Leng Tan, Mark Rosenthal
May 23, 2013·The New England Journal of Medicine·Peter D SlyAREST CF Investigators
Aug 21, 2013·The Journal of Experimental Medicine·Zamaneh MikhakAndrew D Luster
Sep 10, 2013·Immunity·Gregory F SonnenbergD Artis
Dec 11, 2013·The Journal of Experimental Medicine·Maryam SalimiGraham Ogg
Dec 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Emily HamsPadraic G Fallon
Jun 11, 2014·Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology·J Mjösberg, L Eidsmo
Jun 28, 2014·The European Respiratory Journal·Kerstin TiringerThomas Eiwegger
Aug 21, 2014·Mucosal Immunology·D Sj AllanJ R Carlyle
Aug 31, 2014·The Journal of Allergy and Clinical Immunology·Kathleen R BartemesHirohito Kita
Sep 23, 2014·Immunity·Andreas DiefenbachShigeo Koyasu
Apr 19, 2015·Biomedical Engineering Online·Adma N LimaPedro L Melo
May 2, 2015·The European Respiratory Journal·Luke W GarrattAustralian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF)
Oct 17, 2015·Science·Georg GasteigerAlexander Y Rudensky
Jan 5, 2016·PloS One·Katrien C De GroveGuy G Brusselle
Jan 31, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Florence RoanSteven F Ziegler
Feb 10, 2016·Clinics in Chest Medicine·Emanuela M Bruscia, Tracey L Bonfield
Feb 19, 2016·European Journal of Immunology·Hye Young KimRosemarie H Dekruyff

Related Concepts

CCL20 protein, human
CCR6 protein, human
Lymphoid Cells
Mouse Model

Related Feeds

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.