Lung inflammation stalls Th17-cell migration en route to the central nervous system during the development of experimental autoimmune encephalomyelitis.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Kanayama, M; Danzaki, K; He, Y-W; Shinohara, ML

Published Date

  • September 2016

Published In

Volume / Issue

  • 28 / 9

Start / End Page

  • 463 - 469

PubMed ID

  • 26989091

Pubmed Central ID

  • PMC5006092

Electronic International Standard Serial Number (EISSN)

  • 1460-2377

Digital Object Identifier (DOI)

  • 10.1093/intimm/dxw013


  • eng

Conference Location

  • England