title: Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis.
abstract: Recruiting pathogenic T cells to the central nervous system (CNS) is a critical step during the development of experimental autoimmune encephalomyelitis (EAE). Here, we report that the absence of autophagy and microtubule-associated protein 1A/1B-light chain 3-associated phagocytosis significantly delayed the onset of EAE in Atg7 conditional knockout (Atg7 CKO) mice in myeloid cells. T-helper cell-cell priming appeared to be normal in the Atg7 CKO mice, but the mice showed significant accumulation of Th17 cells in the lung. The data suggested that the stalling of Th17 cells in the lung en route to the CNS caused the delay. The lung of Atg7 CKO mice, in which we previously demonstrated spontaneous mild inflammation, showed high expression of CCL20, a chemokine that attracts Th17 cells. We have also shown that LPS intranasal instillation delayed EAE onset, suggesting that pulmonary inflammation has an impact on EAE development. Based on our data, therapeutic immunomodulation targeted to the lung, rather than systemically, might be a possible future option to treat multiple sclerosis.
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kanayama
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Keiko
authors.initials: K
authors.lastname: Danzaki
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
authors.affiliation: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA mari.shinohara@duke.edu.
authors.forename: Mari L
authors.initials: ML
authors.lastname: Shinohara
mesh_terms: D000818:Animals; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000276:immunology; D002464:Cell Migration Inhibition / Q000235:genetics / Q000276:immunology*; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D054418:Chemokine CCL20 / Q000235:genetics / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D009103:Multiple Sclerosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology*
chemical_list: C502661:Atg7 protein, mouse; C493447:CCL20 protein, mouse; D054418:Chemokine CCL20; D008070:Lipopolysaccharides; D000071193:Autophagy-Related Protein 7
keywords: CCL20; T-cell recruitment; autoimmunity; autophagy