Epidermal Langerhans cells are not required for UV-induced immunosuppression
Open accessAbstract
UV light can be highly beneficial in the treatment of skin disorders such as psoriasis. It is thought to cause immunosuppression by depleting or altering the function of epidermal Langerhans cells (LC). Our previous studies identified a novel langerin+ dendritic cell in the dermis, distinct from LC in phenotype, circulation, and function. In this study, we determined the role of LC and dermal langerin+ cells in UV suppression. UV light suppressed the CD8 T cell response to both contact hypersensitivity and epicutaneous protein immunization, and resulted in a dramatically altered phenotype of LC. UV light did not alter early CD8 T cell activation in the lymph nodes, but rather reduced CD8 T cell expansion at later time points. We found that dermal langerin+ cells, but not LC, were essential for the CD8 T cell response. Furthermore, in the selective absence of LC, UV light still caused suppression of both CD8 T cell expansion and contact hypersensitivity.
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Defects in immune surveillance might result from the generation of tolerogenic LCs or dermal dendritic cells by UV-induced apoptotic cells, with subsequent activation of Treg cells and depletion of CD8+ T cells.
“The defects in immune surveillance might result from the generation of tolerogenic LCs or dermal dendritic cells [125] by UV-induced apoptotic cells, with subsequent activation of Treg cells and depletion of CD8+ T cells [65].”
From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [125]
The Results and Discussion report that UV alters LC phenotype and that LCs may contribute to immunosuppression, although they are not required for it. The paper does not show that UV-induced apoptotic cells generate tolerogenic LCs or dermal dendritic cells. The later Treg and CD8+ T-cell clause carries a different citation in the citing sentence. (LLM, conf=0.78)
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Cites
T cell receptor antagonist peptides induce positive selection.
Hogquist, K., Jameson, S., Heath, W., Howard, J. L., Bevan, M., & Carbone, F. (1994) · Cell · doi:10.1016/0092-8674(94)90169-4 · Cited by 3,252 · see citing works
Self-citationKissenpfennig, A., Henri, S., Dubois, B., Laplace-Builhé, C., Perrin, P., Romani, N., Tripp, C. H., Douillard, P., Leserman, L., Kaiserlian, D., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.004 · Cited by 1,041 · cited 7× · see citing works
“(14) to investigate the effect of UV on epidermal LC in vivo.”
InfluentialToews, G., Bergstresser, P., & Streilein, J. (1980) · Journal of Immunology · doi:10.4049/jimmunol.124.1.445 · Cited by 963 · cited 3× · see citing works
“The number (4, 26), migration (2, 27–29), phenotype (17–19), and Ag-presenting properties (18, 19) of LC have all been shown to be altered by UV treatment.”
Cross-presentation of viral and self antigens by skin-derived CD103+ dendritic cells
Bedoui, S., Whitney, P. G., Waithman, J. C., Eidsmo, L., Wakim, L. M., Caminschi, I., Allan, R. S., Wojtasiak, M., Shortman, K., Carbone, F., et al. (2009) · Nature Immunology · doi:10.1038/ni.1724 · Cited by 707 · see citing works
Epidermal langerhans cell-deficient mice develop enhanced contact hypersensitivity.
Kaplan, D., Jenison, M., Saeland, S., Shlomchik, W. D., & Shlomchik, M. (2005) · Immunity · doi:10.1016/j.immuni.2005.10.008 · Cited by 601 · cited 3× · see citing works
“However, this premise has been challenged recently by analysis of CHS in mice in which epidermal LC were either conditionally depleted (14, 24) or permanently ablated (13).”
Identification of a novel population of Langerin+ dendritic cells
Bursch, L. S., Wang, L.-C., Igyártó, B., Kissenpfennig, A., Malissen, B., Kaplan, D., & Hogquist, K. (2007) · Journal of Experimental Medicine · doi:10.1084/jem.20071966 · Cited by 570 · see citing works
Self-citationGeurtsvankessel, C., Willart, M., van Rijt, L. V., Muskens, F., Kool, M., Baas, C., Thielemans, K., Bennett, C. L., Clausen, B., Hoogsteden, H., et al. (2008) · Journal of Experimental Medicine · doi:10.1084/jem.20071365 · Cited by 541 · see citing works
Fabo, E. C. D., & Noonan, F. P. (1983) · The Journal of Experimental Medicine · doi:10.1084/jem.158.1.84 · Cited by 522 · cited 1× · see citing works
“Indeed, several soluble mediators have been shown to contribute to UV suppression, including IL-10 (30–32), TNF- (30), calcitonin generelated peptide (30), cis-urocanic acid (33), prostaglandins (34), and others (3).”
Blood-derived dermal langerin+ dendritic cells survey the skin in the steady state
Ginhoux, F., Collin, M., Bogunovic, M., Abel, M., Leboeuf, M., Helft, J., Ochando, J., Kissenpfennig, A., Malissen, B., Grisotto, M., et al. (2007) · Journal of Experimental Medicine · doi:10.1084/jem.20071733 · Cited by 494 · see citing works
Ultraviolet light depletes surface markers of Langerhans cells.
Aberer, W., Schuler, G., Stingl, G., Hönigsmann, H., & Wolff, K. (1981) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12525745 · Cited by 467 · cited 3× · see citing works
“However, UV irradiation did up-regulate the expression of class II MHC and other costimulatory molecules (Fig.”
Poulin, L., Henri, S., de Bovis, B., Devilard, E., Kissenpfennig, A., & Malissen, B. (2007) · Journal of Experimental Medicine · doi:10.1084/jem.20071724 · Cited by 459 · see citing works
Bennett, C. L., van Rijn, E., Jung, S., Inaba, K., Steinman, R., Kapsenberg, M., & Clausen, B. (2005) · Journal of Cell Biology · doi:10.1083/jcb.200501071 · Cited by 459 · cited 2× · see citing works
“In the conditional deficiency models, one group found CHS was decreased (24), whereas the other group did not observe any change (14).”
Origin and Function of Epidermal Langerhans Cells
Stingl, G., Tamaki, K., & Katz, S. I. (1980) · Immunological Reviews · doi:10.1111/j.1600-065x.1980.tb01043.x · Cited by 404 · cited 1× · see citing works
“Epidermal LC had been thought to be the principal APC in the skin to promote both innate and adaptive immune responses (22, 23).”
Shreedhar, V., Giese, T., Sung, V. W., & Ullrich, S. E. (1998) · Journal of Immunology · doi:10.4049/jimmunol.160.8.3783 · Cited by 369 · cited 1× · see citing works
“Indeed, several soluble mediators have been shown to contribute to UV suppression, including IL-10 (30–32), TNF- (30), calcitonin generelated peptide (30), cis-urocanic acid (33), prostaglandins (34), and others (3).”
Mechanisms underlying UV-induced immune suppression.
Ullrich, S. (2005) · Mutation research · doi:10.1016/j.mrfmmm.2004.06.059 · Cited by 332 · cited 2× · see citing works
“Epidermal Langerhans cells (LC) are the predominant dendritic cell (DC) subset in the epidermis and thus are thought to be an important APC affected by UV light in this model (3).”
Haniffa, M., Ginhoux, F., Wang, X.-N., Bigley, V., Abel, M., Dimmick, I., Bullock, S., Grisotto, M., Booth, T., Taub, P., et al. (2009) · Journal of Experimental Medicine · doi:10.1084/jem.20081633 · Cited by 269 · cited 1× · see citing works
“Three prominent DC populations have been described in human skin, epidermal LC, which are CD1a langerin , and two dermal DC populations: one that is CD1a CD14 , the other that is CD14 CD1a (40).”
Langerhans cells – dendritic cells of the epidermis
Romani, N., Holzmann, S., Tripp, C. H., Koch, F., & Stoitzner, P. (2003) · Acta Pathologica, Microbiologica et Immunologica Scandinavica (APMIS) · doi:10.1034/j.1600-0463.2003.11107805.x · Cited by 264 · cited 1× · see citing works
“Epidermal LC had been thought to be the principal APC in the skin to promote both innate and adaptive immune responses (22, 23).”
Nishigori, C., Yarosh, D., Ullrich, S. E., Vink, A., Bucana, C., Roza, L., & Kripke, M. (1996) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.93.19.10354 · Cited by 256 · see citing works
Nagao, K., Ginhoux, F., Leitner, W., Motegi, S., Bennett, C. L., Clausen, B., Merad, M., & Udey, M. (2009) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.0807126106 · Cited by 254 · cited 1× · see citing works
“Langerin DC were recently shown to be required for the CD8 T cell response to influenza in the lung (37), despite the presence of several other DC types, and dermal langerin DC were required for optimal production of -galactosidase-specific IgG2a/c and IgG2b after gene gun immunization (38).”
The role of IL‐4, IL‐10, and TNF‐α in the immune suppression induced by ultraviolet radiation
Rivas, J. M., & Ullrich, S. E. (1994) · Journal of Leukocyte Biology · doi:10.1002/jlb.56.6.769 · Cited by 223 · see citing works
Prevention of UV radiation–induced immunosuppression by IL-12 is dependent on DNA repair
Schwarz, A., Maeda, A., Kernebeck, K., van Steeg, H., Beissert, S., & Schwarz, T. (2005) · Journal of Experimental Medicine · doi:10.1084/jem.20041212 · Cited by 202 · cited 1× · see citing works
“Further studies suggested that the epidermal LC disappearance might result from UV-induced DNA damage (16) and impaired migration from epidermis to s.”
Schwarz, T. (2007) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2007.00223.x · Cited by 197 · cited 1× · see citing works
“Furthermore, the induction of regulatory T cells has been suggested to play a role in UV suppression (35, 36) and the induction of a regulatory T cell response could occur independently of LC.”
Insights into Langerhans cell function from Langerhans cell ablation models
Kaplan, D., Kissenpfennig, A., & Clausen, B. (2008) · European Journal of Immunology · doi:10.1002/eji.200838397 · Cited by 173 · cited 1× · see citing works
“In contrast, evidence is emerging that epidermal LC may also regulate or suppress immune responses (11, 12).”
Tang, A., & Udey, M. (1991) · Journal of Immunology · doi:10.4049/jimmunol.146.10.3347 · Cited by 155 · cited 2×
“The number (4, 26), migration (2, 27–29), phenotype (17–19), and Ag-presenting properties (18, 19) of LC have all been shown to be altered by UV treatment.”
Psoralen and Ultraviolet A Light Therapy for Psoriasis
Stern, R. S. (2007) · New England Journal of Medicine · doi:10.1056/nejmct072317 · Cited by 149 · cited 1× · see citing works
“The effect is thought to be due to UV-induced immunosuppression (1, 2).”
Ullrich, S. E. (1995) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.1995.tb02359.x · Cited by 136 · see citing works
Langerin Expressing Cells Promote Skin Immune Responses under Defined Conditions1
Wang, L.-C., Bursch, L. S., Kissenpfennig, A., Malissen, B., Jameson, S., & Hogquist, K. (2008) · Journal of Immunology · doi:10.4049/jimmunol.180.7.4722 · Cited by 133 · cited 3× · see citing works
“This finding is consistent with previous results from our lab showing that dermal langerin CD103 DC were sufficient to promote CHS (7) and the response to OVA protein when epicutaneously applied (10).”
InfluentialSelf-citationCutting Edge: CD1a+ Antigen-Presenting Cells in Human Dermis Respond Rapidly to CCR7 Ligands1
Angel, C. E., George, E., Brooks, A., Ostrovsky, L., Brown, T. P. L. H., & Dunbar, P. (2006) · Journal of Immunology · doi:10.4049/jimmunol.176.10.5730 · Cited by 127 · see citing works
Shklovskaya, E., Roediger, B., & Groth, B. F. D. S. (2008) · Journal of Immunology · doi:10.4049/jimmunol.181.1.418 · Cited by 123 · see citing works
Weiss, J. M., Renkl, A. C., Denfeld, R., de Roche, R., Spitzlei, M., Schöpf, E., & Simon, J. (1995) · European Journal of Immunology · doi:10.1002/eji.1830251022 · Cited by 114 · cited 2× · see citing works
“The number (4, 26), migration (2, 27–29), phenotype (17–19), and Ag-presenting properties (18, 19) of LC have all been shown to be altered by UV treatment.”
Ghoreishi, M., & Dutz, J. (2006) · Journal of Immunology · doi:10.4049/jimmunol.176.4.2635 · Cited by 90 · see citing works
Kölgen, W., Both, H., van Weelden, H., Guikers, K. L. H., Bruijnzeel-Koomen, C. A. F. M., Knol, E. F., van Vloten, W. A., & de Gruijl, F. R. (2002) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.2002.01742.x · Cited by 88 · see citing works
Obata, M., & Tagami, H. (1985) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12275379 · Cited by 72 · cited 1×
“The number (4, 26), migration (2, 27–29), phenotype (17–19), and Ag-presenting properties (18, 19) of LC have all been shown to be altered by UV treatment.”
Ultraviolet B radiation-induced immunosuppression: molecular mechanisms and cellular alterations
Schade, N., Esser, C., & Krutmann, J. (2005) · Photochemical and Photobiological Sciences · doi:10.1039/b418378a · Cited by 71 · cited 1× · see citing works
“Furthermore, the induction of regulatory T cells has been suggested to play a role in UV suppression (35, 36) and the induction of a regulatory T cell response could occur independently of LC.”
Langerhans cells are not required for efficient skin graft rejection.
Obhrai, J., Oberbarnscheidt, M., Zhang, N., Mueller, D., Shlomchik, W. D., Lakkis, F. G., Shlomchik, M., & Kaplan, D. (2008) · Journal of Investigative Dermatology · doi:10.1038/jid.2008.52 · Cited by 62 · cited 12×
“These procedures were conducted as previously described (11).”
InfluentialCells with UV-specific DNA damage are present in murine lymph nodes after in vivo UV irradiation.
Sontag, Y., Guikers, C. L. H., Vink, A., de Gruijl, F. D., van Loveren, H., Garssen, J., Roza, L., Kripke, M., van der Leun, J. C., & van Vloten, W. V. (1995) · Journal of Investigative Dermatology · doi:10.1111/1523-1747.ep12606971 · Cited by 61 · see citing works
Cruz, P. D., Tigelaar, R., & Bergstresser, P. (1990) · Journal of Immunology · doi:10.4049/jimmunol.144.7.2486 · Cited by 52 · cited 2×
“However, a gain of function approach, in which LC were UV irradiated and loaded with hapten in vitro, resulted in suppression of immune responses upon reintroduction into animals (6).”
Schwarz, A., Maeda, A., & Schwarz, T. (2007) · Journal of Immunology · doi:10.4049/jimmunol.178.2.877 · Cited by 50 · cited 2× · see citing works
“Furthermore, other gain of function approaches suggested that LC can influence the migration of suppressive regulatory T cells (21).”
Effect of PUVA, narrow-band UVB and cyclosporin on inflammatory cells of the psoriatic plaque
Erkin, G., Uğur, Y., Gürer, C. K., Aşan, E., Korkusuz, P., Şahin, S., & Kölemen, F. (2007) · Journal of Cutaneous Pathology · doi:10.1111/j.1600-0560.2006.00591.x · Cited by 44 · cited 1× · see citing works
“The effect is thought to be due to UV-induced immunosuppression (1, 2).”
McLoone, P., Woods, G., & Norval, M. (2005) · Photochemistry and Photobiology · doi:10.1562/2005-04-10-ra-484 · Cited by 31 · see citing works
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1 of the 41 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- [3]Dandie GW Clydesdale GJ Radcliff FJ Muller HK 2001 Migration of Langerhans cells and gammadelta dendritic cells from UV-B-irradiated sheep skin Immunol Cell Biol 79 41 48 11168622
- [28]Moodycliffe AM Kimber I Norval M 1992 The effect of ultraviolet B irradiation and urocanic acid isomers on dendritic cell migration Immunology 77 394 399 1478685 PMC1421727
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Lee, C.-H., Wu, S.-B., Hong, C.-H., Yu, H.-S., & Wei, Y.-H. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14036414 · Cited by 271 · see citing works
Prasad, R., & Katiyar, S. K. (2017) · Photochemistry and Photobiology · doi:10.1111/php.12687 · Cited by 60 · see citing works
The evolving function of Langerhans cells in adaptive skin immunity
Igyártó, B., & Kaplan, D. (2010) · Immunology and Cell Biology · doi:10.1038/icb.2010.24 · Cited by 38 · see citing works
THE FUNCTIONS OF SKIN LANGERHANS CELLS IN IMMUNE TOLERANCE AND CANCER IMMUNITY
Mirzanov, B. (2025) · Eurasian Journal of Medical and Natural Sciences · doi:10.70413/ejmns-v05-i01-s10726
- Authors
- Wang, L., Jameson, S. C., & Hogquist, K. A.
- Affiliations
- Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota , Minneapolis, MN 55455
- University of Minnesota (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-11-01
- Volume
- 183
- Issue
- 9
- Pages
- 5548-5553
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC2921127
- OpenAlex
- W1856802301
- Cited by
- 49
- References
- 41
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2019: 2 · 2018: 3 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 4 · 2013: 4 · 2012: 3
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (U01AI070380, P01-AI 35296, U01 AI 70380, P01AI035296)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Keywords
- epidermal Langerhans cells, UV-induced immunosuppression, CD8+ T cell responses, contact hypersensitivity, T cell expansion
- MeSH terms
- Epidermal Cells, Administration, Cutaneous, Animals, Antigens, Surface, Dendritic Cells, Dermatitis, Contact, Epidermis, Immunosuppression Therapy, Langerhans Cells, Mice, Inbred C57BL, Mice, Transgenic, Ovalbumin, Ultraviolet Rays, CD8-Positive T-Lymphocytes, Lectins, C-Type, Mannose-Binding Lectins, Mice, Gene Knock-In Techniques
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