The impact of irradiance on UVB-induced cutaneous immunosuppression: Implications on administering most efficient phototherapy.

BACKGROUND: Ultraviolet B (UVB) is commonly used for treating dermatologic conditions. Recently, high irradiance UVB (HIUVB) has been suggested to be more effective for treating skin conditions as compared to its low irradiance (LI) counterpart. The biological impact of UVB radiation emitted at different irradiance on cutaneous immunity remains obscure. OBJECTIVE: This study aimed to explore the impacts of UVB radiation administered at equivalent fluence (mJ/cm2) but different irradiance (mW/cm2) on cutaneous immune response. METHODS: Cultured bone marrow derived dendritic cell (BMDC) were treated with equivalent fluence of UVB radiation with HIUVB or LIUVB. The phenotypic and functional alterations of BMDCs were documented. Animal models were used to validate the in vitro results in vivo and explore the mechanisms involved. RESULTS: After equivalent fluence of UVB radiation, the HIUVB treated BMDC showed significantly lower MHCII and CD86 expressions, reduced capacity to stimulate T cell proliferation, and enhanced activation of aryl hydrocarbon receptor (AhR)-activated genes as compared to control while their LIUVB treated counterpart showed no significant change. Using animal model, the HIUVB induced significantly higher immune suppressive effect in mice as compared to their LIUVB counterpart after equivalent fluence of UVB treatment. The superior immune suppressive effect of HIUVB over LIUVB radiation was not observed when similar experiments were performed using AhR-deficient mice. CONCLUSION: We propose irradiance played an important role modulating UVB-induced cutaneous immune suppression. Future works on UVB phototherapy, both clinical and research, should incorporate this important parameter into consideration.

Regulatory B cells induced by ultraviolet B through toll-like receptor 4 signalling contribute to the suppression of contact hypersensitivity responses in mice.

BACKGROUND: Ultraviolet (UV) B irradiation is known to suppress contact hypersensitivity (CHS) responses in mouse models by suppressing immune responses. However, the cellular mechanisms responsible for UVB-induced systemic suppression remain unclear. Regulatory B cells have been reported to play an inhibitory role during CHS. It is presently unknown whether regulatory B cells contribute to the effect of UVB phototherapy. OBJECTIVE: To investigate the inductive effect of UVB on regulatory B cells and the underlying mechanisms by using a CHS mouse model. METHODS: CHS was induced with oxazolone, and evaluated by histopathology, flow cytometry, and quantitative real-time polymerase chain reaction. RESULT: We found that UVB irradiation induced regulatory B cell expansion and ameliorated CHS. UVB-induced regulatory B cells contribute to systemic immunosuppression by inhibiting the proliferation of T cells. Moreover, we determined that toll-like receptor (TLR) 4, the expression of which was upregulated in B cells after UVB exposure, played an essential role in the induction of regulatory B cells. CONCLUSION: Our data identified regulatory B cells as regulators of UVB-induced immunosuppression in CHS, and suggest the importance of the UVB-TLR4 axis in the generation of regulatory B cells.

Immunomodulatory effects of low-intensity near-infrared laser irradiation on contact hypersensitivity reaction.

BACKGROUND/PURPOSE: Contact hypersensitivity (CHS) reaction is a useful model for studying the skin immune system and inflammatory reactions in the skin. In this study, an experimental model of CHS reaction was employed to assess immunomodulatory effects of near-infrared (near-IR) low-intensity laser (LIL) irradiation, which is used as adjuvant therapy in dermatology, physical medicine, rheumatology, etc., because of its declared anti-inflammatory, biostimulative and analgesic effects. METHODS: The effects of near-IR LIL irradiation (lambda=904 nm, irradiance 60 mW/cm2, fluence 3.6 J/cm2) on CHS reaction to 1-chloro-2,4-dinitrochlorobenzene (DNCB) in Albino Oxford rats were examined by irradiating experimental groups of animals before the induction phase of CHS reaction, while nonirradiated animals and animals that received vehicle instead of hapten served as controls. Ear-swelling assay, histopathological examination of H&E preparations of ear skin, computer-assisted image analysis of dermal infiltrate, ear skin organ culture with the determination of cutaneous production of tumour necrosis factor-alpha (by ELISA assay) and nitric oxide (by Griess' assay) were used for measuring the effects of LIL in the elicitation phase of CHS reaction. Cellularity, dendritic cell content, flow cytometry and proliferation assays (spontaneous and in the presence of IL-2 and concanavalin A) of the draining lymph node cells (DLNC) were performed for the assessment of LIL irradiation effects in the induction phase. RESULTS: In the irradiated group of animals, ear swelling was significantly diminished compared to control animals (101+/-11.5% vs. 58+/-11.6%, P<0.01). This was accompanied by a highly significant decrease in the density of dermal infiltrate (22+/-0.81 vs. 14.2+/-1.75 cells per unit area, P<0.01) and a significant decrease in nitrite levels in the medium conditioned by organ-cultured ear skin (17.63+/-1.91 vs. 3.16+/-1.69 microM NaNO2; P<0.01), while TNF-alpha concentration was not changed. Cellularity and dendritic cell content in DLNC population, as well as the expression of TCR-alpha, CD4, CD8 and CD25, were not changed between irradiated and nonirradiated animals. Proliferation rates of DLNC cultured for 72 h were significantly lower in irradiated animals (17.3+/-4.1 vs. 13.9+/-0.9 x 103 c.p.m.; P<0.01). In cultures of DLNC with added rIL-2 or 0.5 microg/ml of concanavalin A, proliferation rates were also significantly decreased in irradiated animals (34.7+/-3.5 vs. 31.2+/-2. c.p.m. in IL-2-supplemented culture, P<0.01; 70.9+/-6.4 vs. 58.3+/-9.1 x 103 c.p.m. in concanavalin A-supplemented culture, P<0.01). However, this effect was overcome in the presence of the higher concentration of concanavalin A (2.5 microg/ml) (nonirradiated 38.7+/-3.1, irradiated 123.1+/-7.3 x 103 c.p.m., P<0.01). CONCLUSION: LIL irradiation showed a systemic immunomodulatory effect on CHS reaction to DNCB in rats. Decreased ear swelling observed in the elicitation phase was associated with diminished proliferative responses of the DLNC in the induction phase of CHS reaction. Further experimental work is needed to examine the possible mechanisms of these effects.