2011 Fiscal Year Final Research Report
Defining the Langerhans cell niche and the anchoring point
| Project/Area Number |
21689032
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| Research Category |
Grant-in-Aid for Young Scientists (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Dermatology
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| Research Institution | Keio University |
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Principal Investigator |
NAGAO Keisuke 慶應義塾大学, 医学部, 講師 (40286521)
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| Project Period (FY) |
2009 – 2011
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| Keywords | ランゲルハンス細胞 / 毛嚢 / ケモカイン / タイトジャンクション |
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| Research Abstract |
Langerhans cells(LC) are epidermal dendritic cells with incompletely understood origins that associate with hair follicles(HF) for unknown reasons. In this work, we showed that mouse HFs recruited Gr-1high monocyte-derived LC precursors(pre-LCs), whose epidermal entry was CCR2/6 dependent, whereas CCR8 inhibited LC recruitment. Distinct HF regions differentially expressed CCR2/6 ligands. The isthmus expressed CCL2, the infundibulum expressed CCL20, and keratinocytes in the bulge produced the CCR8 ligand, CCL8. Thus, distinct HF keratinocyte subpopulations promote or inhibit LC repopulation via differential chemokine production, a feature also demonstrated in humans. LCs/Pre-LCs failed to enter hairless skin in both mice and humans, establishing HFs as LC portals, a new paradigm in leukocyte trafficking and regulation of skin inflammation(Nat Immunol, in press). To prove the above findings, we generated and characterized TACE/Sox9 mice, which develop progressive alopecia, and have reported mechanisms of hair loss as an independent manuscript(Stem Cells, in press). Furthermore, during this series of work, we functionally characterized LCs. We showed that LCs extend their dendrites through epidermal tight junctions to uptake skin surface bacteria-derived toxin to induce neutralizing antibodies that protected mice from experimental staphylococcal scalded skin syndrome(Ouchi et al. J Exp Med 2011).
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[Journal Article] Stress-induced chemokine production by hair follicles regulate dendritic cell trafficking in skin2012
Author(s)
Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Manabu Ohyama, Takeya Adachi, Daniela Y. Kitashima, Satoshi Ueha, Keisuke Horiuchi, Hideaki Tanizaki, Kenji Kabashima, Akiharu Kubo, Young-hun Cho, Bjorn E. Clausen, Kouji Matsushima, Makoto Suematsu, Glaucia C. Furtado, Sergio A. Lira, Joshua M. Farber, Mark C. Udey, and Masayuki Amagai
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Journal Title
Nature Immunology
Volume: (in press)
Peer Reviewed
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[Journal Article] Langerhans cell antigen capture through tight junctions confers preemptive immunity in experimental staphylococcal scalded skin syndrome2011
Author(s)
Takeshi Ouchi, Akiharu Kubo, Mariko Yokouchi, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Bjorn E. Clausen, Shigeo Koyasu, Masayuki Amagai, and Keisuke Nagao
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Journal Title
The Journal of Experimental Medicine
Volume: 208(22143886)
Pages: 2607-2613
Peer Reviewed
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[Presentation] Dendritic cell trafficking in skin is regulated by hair follicles via chemokine production2012
Author(s)
Keisuke Nagao, Tetsuro Kobayashi, Kazuyo Moro, Kenji Kabashima, Manabu Ohyama, Young-hun Cho, Bjorn E. Clausen, Mark C. Udey, and Masayuki Amagai
Organizer
75^<th> Annual Meeting for Society for Investigative Dermatology
Place of Presentation
Raleigh, NC, USA
Year and Date
20120509-12
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[Presentation] Langerhans cells play an essential role in inducing protective humoral immune response subsequent to antigen uptake through tight junctions2011
Author(s)
Takeshi Ouchi, Akiharu Kubo, Takeya Adachi, Tetsuro Kobayashi, Daniela Y. Kitashima, Hideki Fujii, Bjoern E. Clausen, Shigeo Koyasu, Masayuki Amagai, and Keisuke Nagao
Organizer
41th Annual ESDR meeting
Place of Presentation
Barcelona, Spain
Year and Date
20110906-10
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