Abstract
Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/ Birbeck granules. TJs at KC-KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC-KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
| Original language | English |
|---|---|
| Pages (from-to) | 2937-2946 |
| Number of pages | 10 |
| Journal | Journal of Experimental Medicine |
| Volume | 206 |
| Issue number | 13 |
| DOIs | |
| Publication status | Published - 2009 Dec 21 |
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ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
- Medicine(all)
Cite this
External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers. / Kubo, Akiharu; Nagao, Keisuke; Yokouchi, Mariko; Sasaki, Hiroyuki; Amagai, Masayuki.
In: Journal of Experimental Medicine, Vol. 206, No. 13, 21.12.2009, p. 2937-2946.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - External antigen uptake by Langerhans cells with reorganization of epidermal tight junction barriers
AU - Kubo, Akiharu
AU - Nagao, Keisuke
AU - Yokouchi, Mariko
AU - Sasaki, Hiroyuki
AU - Amagai, Masayuki
PY - 2009/12/21
Y1 - 2009/12/21
N2 - Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/ Birbeck granules. TJs at KC-KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC-KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
AB - Outermost barriers are critical for terrestrial animals to avoid desiccation and to protect their bodies from foreign insults. Mammalian skin consists of two sets of barriers: stratum corneum (SC) and tight junctions (TJs). How acquisition of external antigens (Ags) by epidermal Langerhans cells (LCs) occur despite these barriers has remained unknown. We show that activation-induced LCs elongate their dendrites to penetrate keratinocyte (KC) TJs and survey the extra-TJ environment located outside of the TJ barrier, just beneath the SC. Penetrated dendrites uptake Ags from the tip where Ags colocalize with langerin/ Birbeck granules. TJs at KC-KC contacts allow penetration of LC dendrites by dynamically forming new claudin-dependent bicellular- and tricellulin-dependent tricellular TJs at LC-KC contacts, thereby maintaining TJ integrity during Ag uptake. Thus, covertly under keratinized SC barriers, LCs and KCs demonstrate remarkable cooperation that enables LCs to gain access to external Ags that have violated the SC barrier while concomitantly retaining TJ barriers to protect intra-TJ environment.
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U2 - 10.1084/jem.20091527
DO - 10.1084/jem.20091527
M3 - Article
C2 - 19995951
AN - SCOPUS:73949120263
VL - 206
SP - 2937
EP - 2946
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
SN - 0022-1007
IS - 13
ER -