Modulation of multiple sclerosis by sunlight exposure: Role of cis-urocanic acid
Jorge Correale jcorreale at fleni.org.ar , Mauricio F. Farez
Received 16 March 2013; published online 24 June 2013.
The role of cis-urocanic acid (UCA) as a UV-mediated immunomodulator in MS patients was investigated. Plasma levels of cis-UCA were significantly lower in MS patients compared to controls. Stimulation of MBP- and MOG-specific T cells in the presence of cis-UCA, significantly increased IL-10, and inhibited IFN-γ production. PBMCs cultured in the presence of cis-UCA increased CD4+CD25+FoxP3+ regulatory T cell percentages. Dendritic cells cultured in the presence of cis-UCA significantly reduced Ag presentation capacity. Finally, cis-UCA activated the 5-HT2A receptor, inducing the increase in phosphorylated forms of ERK 1/2 and JNK2. Thus, in addition to vitamin D, cis-UCA also appears to be an additional UV-mediated immunomodulator.
Highlights (by publisher)
- Relapsing remitting MS patients had significantly lower levels of cis-UCA.
- cis-UCA increased IL-10 secretion and inhibited IFN-γ production by T cells.
- cis-UCA increased the number of CD4+CD25+FoxP3+ regulatory T cells.
- cis-UCA reduced Ag presentation capacity by dendritic cells.
Comments by Vitamin D Life
- This may explain why UV appears to be more important than vitamin D in treating MS
- This may explain why people believe that you should not take a shower after being in the sun
urocanic acid is in the sweat, vs vitamin D is below the surface of the skin
See also Vitamin D Life
- Beneficial effects of UV radiation other than via vitamin D production – June 2012
- Overview of UV and Vitamin D
- Overview MS and vitamin D
- MS prevention by UV is 2X better than prevention by vitamin D levels – Jan 2012
- There is more in UV than vitamin D which suppresses MS in mice – April 2010
- UV produces more than vitamin D – Aug 2011
- Lack of UV 20X more associated with MS than any other variable – Dec 2010
Items in both categories MS and UV are listed here: __
- Sun reduces risk of Multiple Sclerosis via both Vitamin D and another way – Dec 2019
- UV helped EAE mice (MS) designed to not respond to Vitamin D – Oct 2019
- Multiple Sclerosis 2X more likely if low winter UV – June 2018
- Multiple Sclerosis half as likely if get plenty of sunshine (not a news item) – March 2018
- Clinically Isolated Syndrome progresses to Multiple Sclerosis, unless UVB treatments – RCT Dec 2017
- Vitamin D and Sun conference – Germany June 2017
- Multiple Sclerosis suppressed by an Ultraviolet wavelength not associated with Vitamin D (mice) – Nov 2016
- Multiple Sclerosis helped by UV – possibly via cytokines, etc. – Oct 2015
- Hypothesis – Multiple Sclerosis risk increases with low UV, viral infections, and antibiotics in childhood – March 2015
- How UVB reduces autoimmune diseases such as Multiple Sclerosis – April 2014
- UV decreases Multiple Sclerosis via cis-urocanic acid (and via vitamin D) – June 2013
- MS prevention by UV is 2X better than prevention by vitamin D levels – Jan 2012
- There is more in UV than vitamin D which suppresses MS in mice – April 2010
- UV produces more than vitamin D – Aug 2011
- Lack of UV 20X more associated with MS than any other variable – Dec 2010
- Hypothesis - more in sunshine than vitamin D to reduce MS – Feb 2010
- MS UV and Vitamin D – 2009
- Lack of UV increased offspring MS - April 2010
- Mouse MS: UVB but not Vitamin D reduced incidence - April 2010
See also web
- Wikipedia
Urocanic acid was detected in animal sweat and skin where, among other possible functions, it acts as an endogenous sunscreen or photoprotectant against UVB-induced DNA damage. - Cis-urocanic acid, a sunlight-induced immunosuppressive factor, activates immune suppression PNAS 2006 PDF is attached at the bottom of this page
- Clinical Trial: Invasive Bladder Cancer
- Immune System Modulation in Multiple Sclerosis as a Result of Sunlight Exposure: Role of cis-Urocanic Acid (S60.004) Meeting abstract (April 2012?)
Jorge Correale 1 and Mauricio Farez 2 [same authors as the study at the top of this page]
1 Neurology Dr Raul Carrea Institute for Neurological Research Buenos Aires Argentina
2 Dr Raúl Carrea Institute for Neurological Research Buenos Aires Argentina
Objective: To study the role of cis-urocanic acid (UCA) in MS pathogenesis.
Background UCA is a major absorber of UV radiation in the skin. Formed as a trans-isomer from histidine in the upper epidermis, it converts to a systemically-distributed cis-isomer on exposure to sunlight, conferring immunosuppression.
Design/Methods: Ninety-two patients with relapsing remitting MS were examined, fifty-eight patients in remission and 32 during exacerbations. Forty age and gender-matched healthy subjects served as controls. Trans-, and cis-UCA plasma levels were measured by HPLC. MBP- and MOG peptide-specific T cell lines were stimulated with cognate antigens (Ags) in presence and in absence of cis-UCA, whereupon IL-4, IL-10, IL-6, IL-8, IL-17, TGF-β, TNF-α, IFN-{gamma}, and PGE2 were measured using ELISA. CD4+CD25+FoxP3+ regulatory T cells were assessed using flow cytometry.
Results: Plasma levels of cis-UCA were significantly lower in MS patients compared to controls (p= 0.001).
In contrast, no differences in plasma trans-UCA levels were found between groups, nor was any association found between disease activity and plasma cis-UCA levels.
Stimulation of MBP- and MOG-specific T cells with specific Ags in the presence of cis-UCA significantly increased IL-10 and PGE2 secretion, and inhibited IFN-{gamma} production. No effect was observed on the secretion of the other cytokines investigated. Moreover, PBMCs cultured in the presence of cis-UCA increased CD4+CD25+FoxP3+ regulatory T cell percentages 3 to 12-fold. Finally, dendritic cells cultured in the presence of cis-UCA significantly reduced their Ags presentation capacity, when proliferation and cytokines secretion were measured as read-outs of T cell activation.
Conclusions: In addition to Vitamin D, cis-UCA represents an additional UV-mediated immunomodulator, which may help explain the increased prevalence of MS observed at higher latitudes.
Disclosure: Dr. Correale has received personal compensation for activities with Merck Serono Argentina, Biogen Idec, Novartis, and from Teva Neuroscience as a speaker. Dr. Farez has nothing to disclose.
urocanic acid action spectra overlaps that of Vitamin D
Vitamin D spectra is the black dotted line