title: Lung-resident eosinophils represent a distinct regulatory eosinophil subset.
abstract: Increases in eosinophil numbers are associated with infection and allergic diseases, including asthma, but there is also evidence that eosinophils contribute to homeostatic immune processes. In mice, the normal lung contains resident eosinophils (rEos), but their function has not been characterized. Here, we have reported that steady-state pulmonary rEos are IL-5-independent parenchymal Siglec-FintCD62L+CD101lo cells with a ring-shaped nucleus. During house dust mite-induced airway allergy, rEos features remained unchanged, and rEos were accompanied by recruited inflammatory eosinophils (iEos), which were defined as IL-5-dependent peribronchial Siglec-FhiCD62L-CD101hi cells with a segmented nucleus. Gene expression analyses revealed a more regulatory profile for rEos than for iEos, and correspondingly, mice lacking lung rEos showed an increase in Th2 cell responses to inhaled allergens. Such elevation of Th2 responses was linked to the ability of rEos, but not iEos, to inhibit the maturation, and therefore the pro-Th2 function, of allergen-loaded DCs. Finally, we determined that the parenchymal rEos found in nonasthmatic human lungs (Siglec-8+CD62L+IL-3Rlo cells) were phenotypically distinct from the iEos isolated from the sputa of eosinophilic asthmatic patients (Siglec-8+CD62LloIL-3Rhi cells), suggesting that our findings in mice are relevant to humans. In conclusion, our data define lung rEos as a distinct eosinophil subset with key homeostatic functions.
authors.forename: Claire
authors.initials: C
authors.lastname: Mesnil
authors.forename: Stéfanie
authors.initials: S
authors.lastname: Raulier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Paulissen
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Mark A
authors.initials: MA
authors.lastname: Birrell
authors.forename: Dimitri
authors.initials: D
authors.lastname: Pirottin
authors.forename: Thibaut
authors.initials: T
authors.lastname: Janss
authors.forename: Philipp
authors.initials: P
authors.lastname: Starkl
authors.forename: Eve
authors.initials: E
authors.lastname: Ramery
authors.forename: Monique
authors.initials: M
authors.lastname: Henket
authors.forename: Florence N
authors.initials: FN
authors.lastname: Schleich
authors.forename: Marc
authors.initials: M
authors.lastname: Radermecker
authors.forename: Kris
authors.initials: K
authors.lastname: Thielemans
authors.forename: Laurent
authors.initials: L
authors.lastname: Gillet
authors.forename: Marc
authors.initials: M
authors.lastname: Thiry
authors.forename: Maria G
authors.initials: MG
authors.lastname: Belvisi
authors.forename: Renaud
authors.initials: R
authors.lastname: Louis
authors.forename: Christophe
authors.initials: C
authors.lastname: Desmet
authors.forename: Thomas
authors.initials: T
authors.lastname: Marichal
authors.forename: Fabrice
authors.initials: F
authors.lastname: Bureau
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology; D004804:Eosinophils / Q000166:cytology*; D005260:Female; D006706:Homeostasis; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism; D007249:Inflammation; D015848:Interleukin-5 / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D008168:Lung / Q000166:cytology*; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D010587:Phagocytosis; D039981:Pyroglyphidae; D018418:Th2 Cells / Q000166:cytology; D059467:Transcriptome
chemical_list: D000485:Allergens; D015703:Antigens, CD; C093213:CD101 antigen, human; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D019041:L-Selectin