Abstract
Prolonged exposure to ultraviolet light (UV) is known to lead to premature skin ageing, increased incidence of cataract and a high risk of developing skin cancers. UV-B irradiation, even if given as a single suberythemal dose, suppresses some immune responses, possibly reducing the production of T helper (Th) 1 cytokines [interleukin (IL)-2 and interferon-gamma] and augmenting Th2 cytokines (IL-4, IL-5 and IL-10) in mice. We investigated the role of IL-4 in UV-B induced immunomodulation using IL-4 knockout (IL-4 -/-) mice and the parent strain Bb129. Suberythemal UV-B irradiation (1440 J/m2) led to a reduction in the density and antigen presenting ability of Langerhans' cells in the epidermis of both normal and IL-4 -/- mice. Exposure also induced an accumulation of CD4+ and CD8+ lymphocytes as well as dendritic cells in the lymph nodes draining the irradiated site in both strains. The proliferation of lymph node cells in response to the mitogen concanavalin A was enhanced in the IL-4 -/- mice compared with the parent strain. Following UV-B exposure, this proliferation was increased in lymph node cells of parent mice but was significantly suppressed in the IL-4 -/- mice. The contact hypersensitivity (CH) response to oxazolone was suppressed to the same extent by UV-B irradiation in both strains. In the parent mice, infected with herpes simplex virus (HSV) following UV-B exposure and challenged subsequently with inactivated virus, the delayed hypersensitivity (DH) response was suppressed by about 50% compared with unirradiated mice; no such suppression in DH occurred in irradiated IL-4 -/- mice infected with HSV. Thus, IL-4 may be an important mediator of the UV-B-induced suppression in DH but not in CH, where other cytokines may be involved or may compensate for the lack of IL-4.
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Selected References
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- Araneo B. A., Dowell T., Moon H. B., Daynes R. A. 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 Sep 15;143(6):1737–1744. [PubMed] [Google Scholar]
- Beissert S., Hosoi J., Grabbe S., Asahina A., Granstein R. D. IL-10 inhibits tumor antigen presentation by epidermal antigen-presenting cells. J Immunol. 1995 Feb 1;154(3):1280–1286. [PubMed] [Google Scholar]
- Berg D. J., Leach M. W., Kühn R., Rajewsky K., Müller W., Davidson N. J., Rennick D. Interleukin 10 but not interleukin 4 is a natural suppressant of cutaneous inflammatory responses. J Exp Med. 1995 Jul 1;182(1):99–108. doi: 10.1084/jem.182.1.99. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chaker M. B., Tharp M. D., Bergstresser P. R. Rodent epidermal Langerhans cells demonstrate greater histochemical specificity for ADP than for ATP and AMP. J Invest Dermatol. 1984 May;82(5):496–500. doi: 10.1111/1523-1747.ep12261031. [DOI] [PubMed] [Google Scholar]
- El-Ghorr A. A., Pierik F., Norval M. Comparative potency of different UV sources in reducing the density and antigen-presenting capacity of Langerhans cells in C3H mice. Photochem Photobiol. 1994 Sep;60(3):256–261. doi: 10.1111/j.1751-1097.1994.tb05101.x. [DOI] [PubMed] [Google Scholar]
- Gautam S. C., Chikkala N. F., Hamilton T. A. Anti-inflammatory action of IL-4. Negative regulation of contact sensitivity to trinitrochlorobenzene. J Immunol. 1992 Mar 1;148(5):1411–1415. [PubMed] [Google Scholar]
- Goettsch W., Garssen J., de Gruijl F. R., van Loveren H. UV-B and the immune system. A review with special emphasis on T cell-mediated immunity. Thymus. 1993 Mar;21(2):93–114. [PubMed] [Google Scholar]
- Grabbe S., Bruvers S., Granstein R. D. Interleukin 1 alpha but not transforming growth factor beta inhibits tumor antigen presentation by epidermal antigen-presenting cells. J Invest Dermatol. 1994 Jan;102(1):67–73. doi: 10.1111/1523-1747.ep12371734. [DOI] [PubMed] [Google Scholar]
- Grabbe S., Bruvers S., Lindgren A. M., Hosoi J., Tan K. C., Granstein R. D. Tumor antigen presentation by epidermal antigen-presenting cells in the mouse: modulation by granulocyte-macrophage colony-stimulating factor, tumor necrosis factor alpha, and ultraviolet radiation. J Leukoc Biol. 1992 Aug;52(2):209–217. doi: 10.1002/jlb.52.2.209. [DOI] [PubMed] [Google Scholar]
- Howie S., Norval M., Maingay J. Exposure to low-dose ultraviolet radiation suppresses delayed-type hypersensitivity to herpes simplex virus in mice. J Invest Dermatol. 1986 Feb;86(2):125–128. doi: 10.1111/1523-1747.ep12284128. [DOI] [PubMed] [Google Scholar]
- Kopf M., Le Gros G., Bachmann M., Lamers M. C., Bluethmann H., Köhler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature. 1993 Mar 18;362(6417):245–248. doi: 10.1038/362245a0. [DOI] [PubMed] [Google Scholar]
- Moodycliffe A. M., Kimber I., Norval M. The effect of ultraviolet B irradiation and urocanic acid isomers on dendritic cell migration. Immunology. 1992 Nov;77(3):394–399. [PMC free article] [PubMed] [Google Scholar]
- Müller K. M., Jaunin F., Masouyé I., Saurat J. H., Hauser C. Th2 cells mediate IL-4-dependent local tissue inflammation. J Immunol. 1993 Jun 15;150(12):5576–5584. [PubMed] [Google Scholar]
- Noonan F. P., De Fabo E. C., Kripke M. L. Suppression of contact hypersensitivity by UV radiation and its relationship to UV-induced suppression of tumor immunity. Photochem Photobiol. 1981 Dec;34(6):683–689. [PubMed] [Google Scholar]
- Norval M., Simpson T. J., Bardshiri E., Howie S. E. Urocanic acid analogues and the suppression of the delayed type hypersensitivity response to Herpes simplex virus. Photochem Photobiol. 1989 May;49(5):633–639. doi: 10.1111/j.1751-1097.1989.tb08435.x. [DOI] [PubMed] [Google Scholar]
- Rivas J. M., Ullrich S. E. The role of IL-4, IL-10, and TNF-alpha in the immune suppression induced by ultraviolet radiation. J Leukoc Biol. 1994 Dec;56(6):769–775. doi: 10.1002/jlb.56.6.769. [DOI] [PubMed] [Google Scholar]
- Sadlack B., Kühn R., Schorle H., Rajewsky K., Müller W., Horak I. Development and proliferation of lymphocytes in mice deficient for both interleukins-2 and -4. Eur J Immunol. 1994 Jan;24(1):281–284. doi: 10.1002/eji.1830240144. [DOI] [PubMed] [Google Scholar]
- Salerno A., Dieli F., Sireci G., Bellavia A., Asherson G. L. Interleukin-4 is a critical cytokine in contact sensitivity. Immunology. 1995 Mar;84(3):404–409. [PMC free article] [PubMed] [Google Scholar]
- Simon J. C., Cruz P. D., Jr, Bergstresser P. R., Tigelaar R. E. Low dose ultraviolet B-irradiated Langerhans cells preferentially activate CD4+ cells of the T helper 2 subset. J Immunol. 1990 Oct 1;145(7):2087–2091. [PubMed] [Google Scholar]
- Simon J. C., Mosmann T., Edelbaum D., Schopf E., Bergstresser P. R., Cruz P. D., Jr In vivo evidence that ultraviolet B-induced suppression of allergic contact sensitivity is associated with functional inactivation of Th1 cells. Photodermatol Photoimmunol Photomed. 1994 Oct;10(5):206–211. [PubMed] [Google Scholar]
- Takashima A., Bergstresser P. R. Impact of UVB radiation on the epidermal cytokine network. Photochem Photobiol. 1996 Apr;63(4):397–400. doi: 10.1111/j.1751-1097.1996.tb03054.x. [DOI] [PubMed] [Google Scholar]
- Thomson J. A., Troutt A. B., Kelso A. Contact sensitization to oxazolone: involvement of both interferon-gamma and interleukin-4 in oxazolone-specific Ig and T-cell responses. Immunology. 1993 Feb;78(2):185–192. [PMC free article] [PubMed] [Google Scholar]
- Ullrich S. E. The role of epidermal cytokines in the generation of cutaneous immune reactions and ultraviolet radiation-induced immune suppression. Photochem Photobiol. 1995 Sep;62(3):389–401. doi: 10.1111/j.1751-1097.1995.tb02359.x. [DOI] [PubMed] [Google Scholar]
- el-Ghorr A. A., Norval M. A monoclonal antibody to cis-urocanic acid prevents the ultraviolet-induced changes in Langerhans cells and delayed hypersensitivity responses in mice, although not preventing dendritic cell accumulation in lymph nodes draining the site of irradiation and contact hypersensitivity responses. J Invest Dermatol. 1995 Aug;105(2):264–268. doi: 10.1111/1523-1747.ep12318410. [DOI] [PubMed] [Google Scholar]
- el-Ghorr A. A., Norval M. The effect of chronic treatment of mice with urocanic acid isomers. Photochem Photobiol. 1997 May;65(5):866–872. doi: 10.1111/j.1751-1097.1997.tb01936.x. [DOI] [PubMed] [Google Scholar]
