Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes

Silberberg-Sinakin, Inga; Thorbecke, G. J.; Baer, Rudolf L.; Rosenthal, Stanley A.; Berezowsky, Vera

doi:10.1016/0008-8749(76)90105-2

Cited by 455 publications

(156 citation statements)

References 9 publications

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“…Previous evidence for migration of LC from the epidermis to regional LN has been derived from contact sensitization and skin transplantation experiments [8,10,25] . However, it is difficult to exc1ude that contact allergens, due to their small size, get to the LN independently and are taken up by resident dendritic cells, or that the effect is caused by dermal dendritic cells.…”

Section: Discussionmentioning

confidence: 99%

Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

et al. 1993

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Murine epidermal Langerhans cells (LC) have been shown to internalizeLeishmania major, a cause of human cutaneous leishmaniasis, and to stimulate a vigorous parasite-specific T cell response. The present study emphasizes the critical role of LC in leishmaniasis by documenting directly that LC have the ability to transport L. major from the skin to the draining lymph node (LN). This was revealed by irreversible labeling of LC with a fluorescent cell linker and in vivo tracking. In contrast, no migration to the LN was seen with L. majorinfected macrophages. These findings were consistent with the results of mixed labeling immunohistology showing that early in infection the expression of parasite antigen in the LN draining the lesion was confined to dendritic cells and could not be detected in macrophages. Furthermore, dendritic cells in LN draining the site of cutaneous infection stimulated L. major-primed T cells in vitro and, most notably, were able to activate unprimed T cells capable of mediating parasite-specific delayed-type hypersensitivity reactivity in vivo . Taken together, the results indicate that LC capture L. major in the skin and transport it to the regional LN for initiation of the specific T cell immune response.

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Section: Discussionmentioning

confidence: 99%

Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

et al. 1993

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“…When LCs encounter exogenous Ags, including haptens and microorganisms, they capture and process them to generate MHC/peptide complexes on their surface. LCs migrate from the epidermis to draining lymphoid tissues to initiate naive T cells and present the MHC/ peptide complexes to T cells with the necessary adhesion molecules and costimulatory signals (1)(2)(3)(4)(5)(6)(7). During this migration, LCs mature from a dormant into an activated functional state.…”

Section: Endritic Cells (Dcs)mentioning

confidence: 99%

Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate 1 Regulates the Migration of Langerhans Cells from the Epidermis to Draining Lymph Nodes

Fukunaga

Nagai

Noguchi

et al. 2004

The Journal of Immunology

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Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) is a member of the signal regulatory protein family in which the extracellular region interacts with its ligand, CD47. Recent studies have demonstrated that SHPS-1 plays an important role in cell migration and cell adhesion. We demonstrate in this study, using immunohistochemical and flow cytometric analyses, that murine Langerhans cells (LCs) express SHPS-1. Treatment of mice ears with 2,4-dinitro-1-fluorobenzene significantly reduced the number of epidermal LCs, and that reduction could be reversed by pretreatment with mAb to SHPS-1 or the CD47-Fc fusion protein. Treatment with the SHPS-1 mAb in vivo reduced the number of FITC-bearing cells in the lesional lymph nodes after the application of FITC to the skin. The SHPS-1 mAb inhibited the in vivo TNF-α-induced migration of LCs. The emigration of dendritic cells expressing I-Ab+ from skin explants to the medium was also reduced by the SHPS-1 mAb. We further demonstrate that the chemotaxis of a murine dendritic cell line, XS52, by macrophage inflammatory protein-3β was significantly inhibited by treatment with the SHPS-1 mAb or CD47-Fc recombinant protein. Finally, we show that migration of LCs was attenuated in mutant mice that lack the intracellular domain of SHPS-1. These observations show that the ligation of SHPS-1 with the SHPS-1 mAb or with CD47-Fc abrogates the migration of LCs in vivo and in vitro, which suggests that the SHPS-1-CD47 interaction may negatively regulate LC migration.

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“…When LC encounter exogenous antigens, including haptens and microorganisms, they capture and process them to generate MHC/peptide complexes on their surface. LC migrate from the epidermis to draining lymphoid tissues in order to initiate naive T cells and to present the MHC/peptide complexes to T cells with the necessary adhesion molecules and costimulatory signals [1][2][3][4][5][6][7]. During this migration, LC mature from a dormant into an activated functional state and down-regulate their endocytotic activity.…”

Section: Introductionmentioning

confidence: 99%

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

Fukunaga

Nagai

et al. 2006

Eur J Immunol

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Recently, we reported that Src homology 2 domain-containing protein tyrosine phosphatase substrate 1 (SHPS-1) plays an important role in the migration of Langerhans cells (LC). Here, we show that SHPS-1 is involved in the maturation of LC. Immunofluorescence analysis on epidermal sheets for I-A or CD86 revealed that LC maturation induced by 2,4-dinitro-1-fluorobenzene (DNFB) or by TNF-a was inhibited by pretreatment with an anti-SHPS-1 monoclonal antibody (mAb) or with CD47-Fc fusion protein, a ligand for SHPS-1. Further, FACS analysis demonstrated that I-A + LC that had emigrated from skin explants expressed CD80 or CD86, whereas CD47-Fc protein reduced CD80 high+ or CD86 high+ cells. CD47-Fc protein also reduced the upregulation of surface CD80 or CD86 by LC remaining in the skin explants. In SHPS-1 mutant mice, we observed that the up-regulation of surface CD86 and CCR7 by LC induced by DNFB as well as that of surface CD80 and CD86 by LC in skin explants was attenuated. Finally, contact hypersensitivity (CHS) response was suppressed in SHPS-1 mutant mice and in wild-type mice treated with an anti-SHPS-1 mAb. These observations indicate that SHPS-1 plays an important role in the maturation of LC ex vivo and in vivo, and that SHPS-1-CD47 interaction may negatively regulate CHS. IntroductionDC are potent antigen-presenting cells that play a crucial role in the initiation of immune responses to pathogens. Langerhans cells (LC) are specialized immature DC in the skin that reside in the suprabasal layers of the epidermis. When LC encounter exogenous antigens, including haptens and microorganisms, they capture and process them to generate MHC/peptide complexes on their surface. LC migrate from the epidermis to draining lymphoid tissues in order to initiate naive T cells and to present the MHC/peptide complexes to Correspondence: Dr. Tatsuya Horikawa, Division of Dermatology, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, 650-0017Japan Fax:+81-78-382-6149 e-mail: thorikaw@med.kobe-u.ac.jp Received 12/1/06Revised 13/9/06 Accepted 19/10/06 [DOI 10.1002/eji.200635864] Key words: Contact hypersensitivity Á Langerhans cells Á Maturation Á Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1Abbreviations: CCR7: CC chemokine receptor 7 Á CHS: contact hypersensitivity Á DNFB: 2,4-dinitro-1-fluorobenzene Á LC: Langerhans cell Á SHPS-1: Src homology 2 domaincontaining protein tyrosine phosphatase substrate 1 Á SIRP a1: signal-regulatory protein a1 and . In mice, SHPS-1 is expressed in myeloid cells, including monocytes, macrophages and DC [25]. SHPS-1 is a transmembrane glycoprotein whose extracellular domain comprises three immunoglobulin-like domains with multiple N-linked glycosylation sites, while the cytoplasmic domain of SHPS-1 contains four tyrosine residues that form two ITIM [26]. SHPS-1 was initially discovered as a tyrosine-phosphorylated transmembrane protein that binds SHP-1 or SHP-2. IAP/CD47, an integrin-associated...

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Antigen-bearing Langerhans cells in skin, dermal lymphatics and in lymph nodes

Cited by 455 publications

References 9 publications

Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

Langerhans cells transport Leishmania major from the infected skin to the draining lymph node for presentation to antigen‐specific T cells

Src Homology 2 Domain-Containing Protein Tyrosine Phosphatase Substrate 1 Regulates the Migration of Langerhans Cells from the Epidermis to Draining Lymph Nodes

Src homology 2 domain‐containing protein tyrosine phosphatase substrate 1 regulates the induction of Langerhans cell maturation

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