UVB exposure-induced systemic modulation of Th1- and Th2-mediated immune responses
Open accessAbstract
Exposure to ultraviolet light, especially UVB wavelengths, can impair immune responses in animals and humans. It is remarkable that this immunomodulation is not restricted to the exposed skin but is also found at other sites, i.e. systemic (distant) immunosuppression. A frequently proposed hypothesis is that UVB exposure inhibits, specifically, T helper 1 (Th1)‐mediated immune responses. The major reason for this is that contact hypersensitivity (CHS) and delayed‐type hypersensitivity (DTH), both Th1‐mediated immune responses, are very sensitive to UVB. For this reason these models are frequently used for photoimmunology studies. In the present study, the effects of UVB exposure were investigated in classical models for Th1‐mediated immunity, i.e. CHS models in which picrylchloride or oxazolone were used as low‐molecular‐weight chemical antigens. In these models, CHS responsiveness and cytokines were measured, the latter by both reverse transcription–polymerase chain reaction (RT–PCR) and enzyme‐linked immunosorbent assay (ELISA). The CHS responses to both contact sensitizers (picrylchloride and oxazolone) were suppressed significantly by pre‐exposure to repeated suberythemal UVB exposure. Interferon‐γ (IFN‐γ), interleukin (IL)‐12 and IL‐4, but not IL‐10, were detectable in spleen and draining lymph nodes of sensitized BALB/c mice. Repeated UVB exposure prior to sensitization at a distant locus inhibited both IFN‐γ and IL‐12 but not IL‐4. In BALB/c mice sensitized with ovalbumin (OVA) in the absence of complete Freund’s adjuvant, a model for Th2‐mediated immunity, OVA‐specific serum IgE and cytokine profiles in the spleen were analysed. Sensitization did lead to a significant increase in OVA‐specific IgE serum titres. Pre‐exposure to UVB resulted in a decreased OVA‐specific IgE serum titre. Both RT–PCR and ELISA showed increased levels of IFN‐γ, IL‐4 and IL‐10 in the spleens of OVA‐sensitized mice. The production of IFN‐γ and IL‐4 was not affected by UVB pre‐exposure. In contrast, the production of IL‐10 was significantly increased. This was probably caused by an up‐regulation of Th2 cells. It is remarkable that IFN‐γ is significantly suppressed by UVB in Th1‐mediated immune reactions but not in Th2‐mediated immune reactions where it even appears to increase. IL‐10, which is up‐regulated by UVB pre‐exposure and produced by, among others, Th2 cells, may represent a shift from Th1‐ to Th2‐mediated immune mechanisms. However, IL‐10 can also inhibit Th2 responses, which might be the reason for a decreased IgE titre in the Th2 model. From the results of this study it is concluded that UVB exposure prior to sensitization/immunization not only inhibits Th1‐mediated but also Th2‐mediated immune responses.
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In T cells, UVB can eliminate the mRNA of IL-12 and decrease interferon-gamma producing T-cells by over 50%.
“In T cells, UVB can eliminate the mRNA of IL-12 and decrease interferon-gamma (IFN-) producing T-cells by over 50% [71,72].”
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 [71]
The Results report reduced cytokine mRNA expression and suppressed IFN-γ production after UVB pre-exposure in sensitized mice; the Discussion also reports suppression of IL-12 in contact-hypersensitivity models. Neither passage says that IL-12 mRNA was eliminated in T cells or that the number of IFN-γ-producing T cells fell by over 50%. (LLM, conf=0.88)
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- [1]Hurks M, Garssen J, Van Loveren H, Vermeer BJ. General aspects of UV-irradiation on the immune system. In: Jori G, editor. Photobiology in Medicine. New York: Plenum Press; 1994. p. 161. [Google Scholar]
- [2]Kripke ML. Immunologic mechanisms in UV-radiation carcinogenesis. Adv Cancer Res. 1981;34:69. doi: 10.1016/s0065-230x(08)60239-0. [DOI] [PubMed] [Google Scholar] · DOI
- [3]Garssen J, Van der Vliet H, De Klerk A, et al. A rat cytomegalovirus infection model as a tool for immunotoxicity testing. Eur J Pharmacol Environ Toxicol. 1995;292:223. doi: 10.1016/0926-6917(95)90026-8. [DOI] [PubMed] [Google Scholar] · DOI
- [4]Giannini MSH. Suppression of pathogenesis in cutaneous Leishmaniasis by UV-irradiation. Infect Immunol. 1986;51:838. doi: 10.1128/iai.51.3.838-843.1986. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [5]Gilmour JW, Norval M. The effect of UVB irradiation, cis-urocanic acid and tumour necrosis factor-α on delayed hypersensitivity to herpes simplex virus. Photodermatol Photoimmunol Photomed. 1993;9:250. [PubMed] [Google Scholar]
- [6]Goettsch W, Garssen J, De Klerk A, et al. Effects of ultraviolet-B exposure on the resistance to Listeria monocytogenes in the rat. Photochem Photobiol. 1996;63:672. doi: 10.1111/j.1751-1097.1996.tb05672.x. [DOI] [PubMed] [Google Scholar] · DOI
- [7]Goettsch W, Garssen J, De Gruijl FR, Van Loveren H. UVB-induced decreased resistance to Trichinella spiralis in the rat is related to impaired cellular immunity. Photochem Photobiol. 1996;64:581. doi: 10.1111/j.1751-1097.1996.tb03108.x. [DOI] [PubMed] [Google Scholar] · DOI
- [8]Goettsch W, Garssen J, Deijns A, De Gruijl FR, Van Loveren H. UVB exposure impairs resistance to infections with Trichinella spiralis. Environ Health Perspec. 1994;102:298. doi: 10.1289/ehp.94102298. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [9]Jeevan A, Kripke ML. Alteration of immune responses to Mycobacterium bovis BCG in mice exposed chronically to low doses of UV radiation. Cell Immunol. 1989;145:2087. doi: 10.1016/0008-8749(90)90159-o. [DOI] [PubMed] [Google Scholar] · DOI
- [10]De Fabo EC, Noonan FP. Mechanism of immune suppression by ultraviolet irradiation in vivo. I. Evidence for the existence of a unique photoreceptor in skin and its role in photoimmunology. J Exp Med. 1983;157:84. doi: 10.1084/jem.158.1.84. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [11]Kripke ML, Cox PA, Alas LG, Yarosh DB. Pyrimidine dimers in DNA initiate systemic immunosuppression in UV-irradiated mice. Proc Natl Acad Sci USA. 1992;89:7516. doi: 10.1073/pnas.89.16.7516. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [12]Boonstra A, Savelkoul HFJ. The role of cytokines in ultraviolet-B induced immunosuppression. Eur Cytokine Netw. 1997;8:117. [PubMed] [Google Scholar]
- [13]Kurimoto I, Streilein JW. Cis-urocanic acid suppression of contact hypersensitivity induction is mediated via tumour necrosis factor-α. J Immunol. 1992;148:3072. [PubMed] [Google Scholar]
- [14]Nishigori C, Yarosh DB, Ullrich SE, et al. Evidence that DNA damage triggers interleukin-10 cytokine production in UV-irradiated murine keratinocytes. Proc Natl Acad Sci USA. 1996;93:10354. doi: 10.1073/pnas.93.19.10354. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [15]Kammeyer MBM, Teunissen MA, de Rie JD, Bos JD. Retention of increased cis-urocanic levels in human body upon UV-B exposure. Photochem Photobiol. 1994;59S doi: 10.1111/j.1751-1097.1997.tb08611.x. [DOI] [PubMed] [Google Scholar] · DOI
- [16]Moodycliffe AM, Norval M, Kimber I, Simpson TJ. Characterisation of a monoclonal antibody to cis-urocanic acid: detection of cis-urocanic acid in the serum of irradiated mice by immunoassay. Immunology. 1993;79:667. [PMC free article] [PubMed] [Google Scholar]
- [17]Sontag Y, Guikers CLH, Vink AA, et al. Cells with UV-specific DNA damage are present in murine lymph nodes after in vivo UV irradiation. J Invest Dermatol. 1995;104:734. doi: 10.1111/1523-1747.ep12606971. [DOI] [PubMed] [Google Scholar] · DOI
- [18]Garssen J, Buckley TL, Van Loveren H. A role for neuropeptides in UVB-induced systemic immunosuppression. Photochem Photobiol. 1998;68:205. [PubMed] [Google Scholar]
- [19]Simon JC, Mosmann T, Edelbaum D, Schopf E, Bergstresser PR, Cruz PD. In vivo evidence that ultraviolet-B-induced suppression of allergic contact sensitivity is associated with functional inactivation of Th1 cells. Photodermatol Photoimmunol Photomed. 1994;10:206. [PubMed] [Google Scholar]
- [20]Mosmann TR, Schumacher JH, Street NF, et al. Diversity of cytokine synthesis and function of mouse CD4+ T cells. Immunol Rev. 1991;123:209. doi: 10.1111/j.1600-065x.1991.tb00612.x. [DOI] [PubMed] [Google Scholar] · DOI
- [21]Araneo BA, Dowel T, Moon HB, Daynes RA. Regulation of murine lymphokine production in vivo. Ultraviolet radiation exposure depresses IL-2 and enhances IL-4 production by T cells through an IL-1 dependent mechanism. J Immunol. 1989;143:1737. [PubMed] [Google Scholar]
- [22]Simon JC, Tigelaar RE, Bergstresser PR, Edelbaum D, Cruz PD. Ultraviolet B radiation converts Langerhans cells from immunogenic to tolerogenic antigen-presenting cells. Induction of specific clonal anergy in CD4+ T helper 1 cells. J Immunol. 1991;146:485. [PubMed] [Google Scholar]
- [23]Goettsch W, Garssen J, De Gruijl FR, Dortant P, Van Loveren H. Methods for exposure of laboratory animals to ultraviolet radiation. Lab Anim. 1999;33:58. doi: 10.1258/002367799780578507. [DOI] [PubMed] [Google Scholar] · DOI
- [24]Sontag Y, Garssen J, De Gruijl FR, Van Der Leun JC, Van Vloten WA, Van Loveren H. Ultraviolet radiation-induced impairment of the early initiating and the late effector phases of contact hypersensitivity to picrylchloride: regulation by different mechanisms. J Invest Dermatol. 1994;102:923. doi: 10.1111/1523-1747.ep12384051. [DOI] [PubMed] [Google Scholar] · DOI
- [25]Hessel EH, Oosterhout AJM, Hofstra CL, et al. Bronchoconstriction and airway hyperresponsiveness after ovalbumin inhalation in sensitized mice. Eur J Pharmacol. 1995;293:401. doi: 10.1016/0926-6917(95)90061-6. [DOI] [PubMed] [Google Scholar] · DOI
- [26]Thomson JA, Troutt AB, Kelso A. Contact sensitization to oxazalone: involvement of both interferon-γ and interleukin-4 in oxazalone-specific Ig and T-cell responses. Immunology. 1993;78:185. [PMC free article] [PubMed] [Google Scholar]
- [27]Hu-Li J, Ohara J, Watson C, Tsang W, Paul WE. Derivation of a T-cell line that is highly responsive to IL-4 and IL-2 and of an IL-2 hyporesponsive mutant of that line (CT.4S) J Immunol. 1989;142:800. [PubMed] [Google Scholar]
- [28]Van Halteren AGS, Van Der Cammen MJF, Biewenga J, Savelkoul HFJ, Kraal G. IgE and mast cell responses upon intestinal allergen exposure. A murine model to study the onset of food allergy. J Allergy Clin Immunol. 1997;1:94. doi: 10.1016/s0091-6749(97)70305-1. [DOI] [PubMed] [Google Scholar] · DOI
- [29]McMichael AJ, Hall AJ. Does immunosuppressive ultraviolet radiation explain the latitude gradient for multiple sclerosis? Epidemiology. 1997;8:642. doi: 10.1097/00001648-199710000-00005. [DOI] [PubMed] [Google Scholar] · DOI
- [30]Noonan FP, Lewis FA. UVB induced immune suppression and infection with Schistosomiasis mansoni. Photochem Photobiol. 1995;61:99. doi: 10.1111/j.1751-1097.1995.tb09249.x. [DOI] [PubMed] [Google Scholar] · DOI
- [31]Salerno A, Dieli F, Sireci G, Bellavia A, Asherson GL. Interleukin-4 is a critical cytokine in contact sensitivity. Immunology. 1995;84:404. [PMC free article] [PubMed] [Google Scholar]
- [32]El-Ghorr AA, Norval M. The role of interleukin-4 in ultraviolet B light-induced immunosuppression. Immunology. 1997;92:26. doi: 10.1046/j.1365-2567.1997.d01-2292.x. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [33]Schwarz A, Grabbe S, Riemann H, et al. In vivo effects of interleukin-10 on contact hypersensitivity and delayed-type hypersensitivity reactions. J Invest Dermatol. 1994;103:211. doi: 10.1111/1523-1747.ep12393073. [DOI] [PubMed] [Google Scholar] · DOI
- [34]Fong TAT, Mosmann TR. The role of IFN-γ in delayed-type hypersensitivity mediated by Th1 clones. J Immunol. 1989;143:2887. [PubMed] [Google Scholar]
- [35]Magram J, Connaughton SE, Warrier RR, et al. IL-12-deficient mice are defective in IFN γ production and type 1 cytokine responses. Immunity. 1996;4:471. doi: 10.1016/s1074-7613(00)80413-6. [DOI] [PubMed] [Google Scholar] · DOI
- [36]Yoshimoto T, Wang CR, Yoneto T, et al. Reduced T helper 1 responses in IL-12 p40 transgenic mice. J Immunol. 1998;160:588. [PubMed] [Google Scholar]
- [37]Xu BH, Aoyama K, Kitani A, Yu S, Matsuyama T, Matsushita T. Interleukin-12 enhances contact hypersensitivity by modulating the in vivo cytokine pattern in mice. J Interferon Cytokine Res. 1998;18:23. doi: 10.1089/jir.1998.18.23. [DOI] [PubMed] [Google Scholar] · DOI
- [38]Enk AH, Salonga J, Becker D, Mohamedzadeh M, Knop J. Induction of hapten-specific tolerance by interleukin 10 in vivo. J Exp Med. 1994;179:1397. doi: 10.1084/jem.179.4.1397. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [39]Fiorentino DF, Bond MW, Mosmann TR. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989;170:2081. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [40]Mosmann TR, Moore KW. The role of IL-10 in crossregulation of Th1 and Th2 responses. Immunol Today. 1991;12:A49. doi: 10.1016/S0167-5699(05)80015-5. [DOI] [PubMed] [Google Scholar] · DOI
- [41]Powrie F, Menon S, Coffman RL. Interleukin-4 and interleukin-10 synergize to inhibit cell-mediated immunity in vivo. Eur J Immunol. 1993;23:2223. doi: 10.1002/eji.1830230926. [DOI] [PubMed] [Google Scholar] · DOI
- [42]Finkelman FD, Holmes J, Katona IM, et al. Lymphokine control of in vivo immunoglobulin isotype selection. Anuu Rev Immunol. 1990;8:303. doi: 10.1146/annurev.iy.08.040190.001511. [DOI] [PubMed] [Google Scholar] · DOI
- [43]Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993;362:245. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar] · DOI
- [44]Michielsen CPPC, Bloksma N, Ultee A, Van Mil F, Vos JG. Hexachlorobenzene-induced immunomodulation and skin and lung lesions: a comparison between Brown Norway, Lewis, and Wistar rats. Toxicol Appl Pharmacol. 1997;144:12. doi: 10.1006/taap.1997.8104. [DOI] [PubMed] [Google Scholar] · DOI
- [45]Seder RA, Gazzinelli R, Sher A, Paul WE. Interleukin-12 acts directly on CD4+ T-cells to enhance priming for interferon-γ production and diminishes interleukin-4 inhibition of such priming. Proc Natl Acad Sci USA. 1993;90:10188. doi: 10.1073/pnas.90.21.10188. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [46]Wynn TA, Morawitz R, Scharton-Kersten T, et al. Analysis of granuloma formation in double cytokine-deficient mice reveals a central role for IL-10 in polarizing both T helper cell 1- and T helper cell 2-type cytokine responses in vivo. J Immunol. 1997;159:5014. [PubMed] [Google Scholar]
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- Authors
- Garssen, Vandebriel, Gruijl, D., Wolvers, Dijk, V., Fluitman, & Loveren, V.
- Affiliations
- National Institute for Public Health and the Environment (NL)
- Utrecht University (NL)
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Garssen
- Venue
- Immunology
- Publisher
- Wiley
- Published
- 1999-07
- Volume
- 97
- Issue
- 3
- Pages
- 506-514
- ISSN
- 0019-2805 (ISSN-L)
- 1365-2567
- PMC
- PMC2326852
- OpenAlex
- W2010626014
- Cited by
- 119
- References
- 0
- Citations by year
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- FWCI
- 10.45
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Immunology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Rivm (National Institute for Public Health and the Environment) (submittedVersion)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- UVB exposure, UV-B radiation, systemic immunosuppression, contact hypersensitivity, delayed-type hypersensitivity, interferon-gamma, IL-12, IL-4, IL-10, ovalbumin-specific IgE, oxazolone, photoimmunology
- MeSH terms
- Animals, Dermatitis, Contact, Enzyme-Linked Immunosorbent Assay, Interferon-gamma, Lymph Nodes, Male, Mice, Inbred BALB C, Ovalbumin, Spleen, Ultraviolet Rays, Interleukin-4, Cytokines, Mice, Knockout, Th1 Cells, Th2 Cells, Reverse Transcriptase Polymerase Chain Reaction, Mice
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