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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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LN Langerin+ LCs express CD1α and CD68 but not CD83 DC–LAMP and CD86. (A) LNs cryostat section from patients with DL were stained with anti-CD83 antibody revealed with Cy5 (blue), FITC-anti-Langerin (green), and PE-anti CD68 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×400; (B) triple immunostaining on DL section using FITC-conjugated Langerin (green), anti-DC–LAMP antibody revealed with Cy5 (blue), and PE-anti CD68 (red) and analyzed by confocal microscopy. Magnification: ×100. (C) Double immunostaining on DL section using FITC anti-CD1a (green) and anti-Langerin revealed with Cy3 (red), and FITC-anti-Langerin (green), and PE-anti CD86 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×100.
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fig2: LN Langerin+ LCs express CD1α and CD68 but not CD83 DC–LAMP and CD86. (A) LNs cryostat section from patients with DL were stained with anti-CD83 antibody revealed with Cy5 (blue), FITC-anti-Langerin (green), and PE-anti CD68 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×400; (B) triple immunostaining on DL section using FITC-conjugated Langerin (green), anti-DC–LAMP antibody revealed with Cy5 (blue), and PE-anti CD68 (red) and analyzed by confocal microscopy. Magnification: ×100. (C) Double immunostaining on DL section using FITC anti-CD1a (green) and anti-Langerin revealed with Cy3 (red), and FITC-anti-Langerin (green), and PE-anti CD86 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×100.

Mentions: To investigate the differentiation state of human DCs after skin lesions, we examined axillary and cervical LNs draining pruritic skin from patients with DL (n = 12, Table I) in comparison with control reactive LNs (RL, n = 10) without history of skin lesion. Patients with DL presented either eczema (n = 3), acne, hidrosadenitis, urticaria, or scabies infection (n = 1 each) or cutaneous lymphoma (n = 5). Control samples were obtained from patients without skin lesion and with reactive axillary and cervical LNs of miscellaneous etiology. Strikingly very large numbers of cells expressing Langerin (CD207), a LC-specific lectin (35, 36), were present in the T cells areas and in the afferent sinuses of all DL LNs (Fig. 1, A–C) . In contrast, Langerin+ cells were very rare or not detectable in inflamed peripheral LNs in the absence of skin lesions (Fig. 1 D). The Langerin+ cells coexpressed CD1a (Fig. 1 B, see also Fig. 2 C) and the LC adhesion molecule E-cadherin, albeit at low levels (Fig. 1 B). Langerin+ cells were localized in close contact with T cells, as evaluated by anti-CD3 staining (Fig. 1 C). Altogether, these features characterize a selective and prominent accumulation of LCs in DL LNs. These features were similar in all 12 DL LNs examined. The predominance of Langerin+ cells in the LN in the presence of skin lesions (Fig. 1, C and D), their location in the afferent sinuses (Fig. 1 A) and the presence of Langerin+ cells containing melanin (unpublished data), suggest that these LCs originate from the skin. Yet, we cannot be exclude that they derive from other, e.g., circulating, precursors.


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)

LN Langerin+ LCs express CD1α and CD68 but not CD83 DC–LAMP and CD86. (A) LNs cryostat section from patients with DL were stained with anti-CD83 antibody revealed with Cy5 (blue), FITC-anti-Langerin (green), and PE-anti CD68 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×400; (B) triple immunostaining on DL section using FITC-conjugated Langerin (green), anti-DC–LAMP antibody revealed with Cy5 (blue), and PE-anti CD68 (red) and analyzed by confocal microscopy. Magnification: ×100. (C) Double immunostaining on DL section using FITC anti-CD1a (green) and anti-Langerin revealed with Cy3 (red), and FITC-anti-Langerin (green), and PE-anti CD86 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×100.
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fig2: LN Langerin+ LCs express CD1α and CD68 but not CD83 DC–LAMP and CD86. (A) LNs cryostat section from patients with DL were stained with anti-CD83 antibody revealed with Cy5 (blue), FITC-anti-Langerin (green), and PE-anti CD68 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×400; (B) triple immunostaining on DL section using FITC-conjugated Langerin (green), anti-DC–LAMP antibody revealed with Cy5 (blue), and PE-anti CD68 (red) and analyzed by confocal microscopy. Magnification: ×100. (C) Double immunostaining on DL section using FITC anti-CD1a (green) and anti-Langerin revealed with Cy3 (red), and FITC-anti-Langerin (green), and PE-anti CD86 (red) and analyzed by confocal microscopy. Representative sections are shown. Original magnification: ×100.
Mentions: To investigate the differentiation state of human DCs after skin lesions, we examined axillary and cervical LNs draining pruritic skin from patients with DL (n = 12, Table I) in comparison with control reactive LNs (RL, n = 10) without history of skin lesion. Patients with DL presented either eczema (n = 3), acne, hidrosadenitis, urticaria, or scabies infection (n = 1 each) or cutaneous lymphoma (n = 5). Control samples were obtained from patients without skin lesion and with reactive axillary and cervical LNs of miscellaneous etiology. Strikingly very large numbers of cells expressing Langerin (CD207), a LC-specific lectin (35, 36), were present in the T cells areas and in the afferent sinuses of all DL LNs (Fig. 1, A–C) . In contrast, Langerin+ cells were very rare or not detectable in inflamed peripheral LNs in the absence of skin lesions (Fig. 1 D). The Langerin+ cells coexpressed CD1a (Fig. 1 B, see also Fig. 2 C) and the LC adhesion molecule E-cadherin, albeit at low levels (Fig. 1 B). Langerin+ cells were localized in close contact with T cells, as evaluated by anti-CD3 staining (Fig. 1 C). Altogether, these features characterize a selective and prominent accumulation of LCs in DL LNs. These features were similar in all 12 DL LNs examined. The predominance of Langerin+ cells in the LN in the presence of skin lesions (Fig. 1, C and D), their location in the afferent sinuses (Fig. 1 A) and the presence of Langerin+ cells containing melanin (unpublished data), suggest that these LCs originate from the skin. Yet, we cannot be exclude that they derive from other, e.g., circulating, precursors.

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