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Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin.

Geissmann F, Dieu-Nosjean MC, Dezutter C, Valladeau J, Kayal S, Leborgne M, Brousse N, Saeland S, Davoust J - J. Exp. Med. (2002)

Bottom Line: This indicates that LC migration and maturation can be independently regulated events.We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation.Immature LCs might regulate immune responses during chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Service d'Anatomie Pathologique, IFR Necker-Enfants Malades, 75015 Paris, France. geissman@necker.fr

ABSTRACT
The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207(+) LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC-lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-beta1, we further found that tumor necrosis factor (TNF)-alpha, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC-LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.

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Cross-linking of Langerin induces the formation of BGs in TNF-α treated LC-type cells. (1–3) LC type-cells were cultured in the presence of GM-CSF, IL-4 (added at day 0 only), TGF-β1 and TNF-α (added at 10 ng/ml for the last 40 h of culture). Inset (1 and 3) show magnification of BGs. Bar = 100 nm on panels 1 and 3 and 1 p.m. on panel 2. (4–7) Cells were cultured as for panels 1–3, and Langerin was cross-linked with mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig for various times. Panel 4 shows the formation of large numbers of gold labeled BGs and coated pits after a very short time (<1 min). Bar = 100 nm. Panels 5–7 show BGs and coated pits at higher magnification. In the absence of TGF-β1 however, TNF-α did not induce the expression of Langerin, nor the formation of BGs (unpublished data). Bar = 100 nm.
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fig4: Cross-linking of Langerin induces the formation of BGs in TNF-α treated LC-type cells. (1–3) LC type-cells were cultured in the presence of GM-CSF, IL-4 (added at day 0 only), TGF-β1 and TNF-α (added at 10 ng/ml for the last 40 h of culture). Inset (1 and 3) show magnification of BGs. Bar = 100 nm on panels 1 and 3 and 1 p.m. on panel 2. (4–7) Cells were cultured as for panels 1–3, and Langerin was cross-linked with mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig for various times. Panel 4 shows the formation of large numbers of gold labeled BGs and coated pits after a very short time (<1 min). Bar = 100 nm. Panels 5–7 show BGs and coated pits at higher magnification. In the absence of TGF-β1 however, TNF-α did not induce the expression of Langerin, nor the formation of BGs (unpublished data). Bar = 100 nm.

Mentions: Electron microscopy confirmed that TNF-α–treated cells have typical LC features as demonstrated by the presence of BGs (Fig. 4 , panels 1–3). To assess whether Langerin is functional in TNF-α–treated cells, we monitored the formation of BGs after Langerin cross-linking. LC-type cells exposed to mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig developed very rapidly (<1 min) high numbers of gold-labeled BGs (Fig. 4, panels 4–7). These data further emphasize that TNF-α induces LCs to express functional Langerin in conjunction with TGF-β1.


Accumulation of immature Langerhans cells in human lymph nodes draining chronically inflamed skin.

Geissmann F, Dieu-Nosjean MC, Dezutter C, Valladeau J, Kayal S, Leborgne M, Brousse N, Saeland S, Davoust J - J. Exp. Med. (2002)

Cross-linking of Langerin induces the formation of BGs in TNF-α treated LC-type cells. (1–3) LC type-cells were cultured in the presence of GM-CSF, IL-4 (added at day 0 only), TGF-β1 and TNF-α (added at 10 ng/ml for the last 40 h of culture). Inset (1 and 3) show magnification of BGs. Bar = 100 nm on panels 1 and 3 and 1 p.m. on panel 2. (4–7) Cells were cultured as for panels 1–3, and Langerin was cross-linked with mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig for various times. Panel 4 shows the formation of large numbers of gold labeled BGs and coated pits after a very short time (<1 min). Bar = 100 nm. Panels 5–7 show BGs and coated pits at higher magnification. In the absence of TGF-β1 however, TNF-α did not induce the expression of Langerin, nor the formation of BGs (unpublished data). Bar = 100 nm.
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Related In: Results  -  Collection

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fig4: Cross-linking of Langerin induces the formation of BGs in TNF-α treated LC-type cells. (1–3) LC type-cells were cultured in the presence of GM-CSF, IL-4 (added at day 0 only), TGF-β1 and TNF-α (added at 10 ng/ml for the last 40 h of culture). Inset (1 and 3) show magnification of BGs. Bar = 100 nm on panels 1 and 3 and 1 p.m. on panel 2. (4–7) Cells were cultured as for panels 1–3, and Langerin was cross-linked with mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig for various times. Panel 4 shows the formation of large numbers of gold labeled BGs and coated pits after a very short time (<1 min). Bar = 100 nm. Panels 5–7 show BGs and coated pits at higher magnification. In the absence of TGF-β1 however, TNF-α did not induce the expression of Langerin, nor the formation of BGs (unpublished data). Bar = 100 nm.
Mentions: Electron microscopy confirmed that TNF-α–treated cells have typical LC features as demonstrated by the presence of BGs (Fig. 4 , panels 1–3). To assess whether Langerin is functional in TNF-α–treated cells, we monitored the formation of BGs after Langerin cross-linking. LC-type cells exposed to mouse anti-Langerin Ab and gold-labeled goat anti–mouse Ig developed very rapidly (<1 min) high numbers of gold-labeled BGs (Fig. 4, panels 4–7). These data further emphasize that TNF-α induces LCs to express functional Langerin in conjunction with TGF-β1.

Bottom Line: This indicates that LC migration and maturation can be independently regulated events.We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation.Immature LCs might regulate immune responses during chronic inflammation.

View Article: PubMed Central - PubMed

Affiliation: Service d'Anatomie Pathologique, IFR Necker-Enfants Malades, 75015 Paris, France. geissman@necker.fr

ABSTRACT
The coordinated migration and maturation of dendritic cells (DCs) such as intraepithelial Langerhans cells (LCs) is considered critical for T cell priming in response to inflammation in the periphery. However, little is known about the role of inflammatory mediators for LC maturation and recruitment to lymph nodes in vivo. Here we show in human dermatopathic lymphadenitis (DL), which features an expanded population of LCs in one draining lymph node associated with inflammatory lesions in its tributary skin area, that the Langerin/CD207(+) LCs constitute a predominant population of immature DCs, which express CD1a, and CD68, but not CD83, CD86, and DC-lysosomal-associated membrane protein (LAMP)/CD208. Using LC-type cells generated in vitro in the presence of transforming growth factor (TGF)-beta1, we further found that tumor necrosis factor (TNF)-alpha, as a prototype proinflammatory factor, and a variety of inflammatory stimuli and bacterial products, increase Langerin expression and Langerin dependent Birbeck granules formation in cell which nevertheless lack costimulatory molecules, DC-LAMP/CD208 and potent T cell stimulatory activity but express CCR7 and respond to the lymph node homing chemokines CCL19 and CCL21. This indicates that LC migration and maturation can be independently regulated events. We suggest that during DL, inflammatory stimuli in the skin increase the migration of LCs to the lymph node but without associated maturation. Immature LCs might regulate immune responses during chronic inflammation.

Show MeSH
Related in: MedlinePlus