Many ME patients feel better in the summer and relapse in winter. I have always presumed that higher levels of vitamin D in the summer from the sun was the explanation. But ME patients with high plasma levels of vitamin D and relapse in the winter made me wonder that something did not add up.
So I searched for answers and I found an article written by Professor Prue Hart, Department of Inflammation, Telethon Institute for Child Health Research, University of Western Australia:
Vitamin D supplementation, moderate sun-exposure and control of immune diseases
The article describes that sun exposure has an immuno suprressive effect that may alleviate disease symptoms in immune diseases. Is this a possibility in ME? I don't know, but I think it is worth while to learn a little more about photoimmunology.
Here are some quotes:
"Abstract: There is considerable debate about the benefits of vitamin D supplementation for multiple sclerosis, allergic asthma, and type 1 diabetes. This has been driven mainly by observational studies linking vitamin D deficiency and insufficiency with increased prevalence of autoimmune and other diseases driven by immune processes. Randomized controlled trials of vitamin D supplementation to treat these (and other) diseases have been disappointing. This review examines the evidence that circulating vitamin D levels provide a surrogate measure of sun exposure and that it is the other molecules and pathways induced by sun exposure, rather than vitamin D-driven processes, that explain many of the benefits often attributed to vitamin D."
"Other than 7-dehydrocholesterol, there are several photoreceptors in skin that absorb UVB photons and have been implicated in UVR-induced immunoregulation."
"Although UVR-induced systemic immunosuppression is more extensively analyzed in mice, suppression of immune responses has been confirmed in humans, and by similar pathways that we believe may be largely independent of vitamin D3 action."
"An important question is how long do the immunoregulatory effects of UVR last. Reduced primary immune responses to chemical antigens in mice remain reduced for up to 3 weeks".
This may explain the relapse in ME patients short after the summer ends (...if photoimmunolgy has a role in ME).
And very important:
"Until the UVR-induced molecules/pathways involved in UVR-induced systemic immunosuppression are confirmed, moderate sun exposure is recommended. "
"Advocacy of moderate sun exposure may enhance the risk of development of UVR-induced skin cancers. Enhanced vigilance and education in identifying skin lesions is recommended. For adults, the benefits of sun exposure versus risk of skin cancer must be considered on an individual basis. However, repeated short sun exposures to a larger body surface area are likely to have a greater effect than longer exposure of smaller areas."
Another article on the subject by Stephen Ullrich and Scott Byrne
The immunologic revolution: photoimmunology gives a good overview over the different immunologic mechanisms of solar exposure. Most of the following knowledge is from the study of UV-radiated mice. I recommend you to read the full article, but for those, who do not have the energy, here is a brief summary:
T regulatory cells: Studies in the 1970’s showed that in addition to being carcinogenic, UV exposure induced immune suppression by T regularory cells. Since then, the photoimmunology has revealed more mechanisms.
Mast cells regulate adaptive immune response: How the immune suppressive signal is transmitted from the skin to the lymph nodes is not entirely clear, but migrating mast cells play a role. UV-irradiation triggers the migration of mast cell from the skin to the lymph nodes. Recruitment of immune modulating mast cells into the dermis peaking at 6h post UV. Mast cells, and mast cell-derived IL-10 inhibits antibody formation by suppressing T follicular helper function.
Solar activated suppressor B cells: Although they do not receive as much attention as T regulatory cells, B cells can also suppress the immune response, primarily by secreting immune regulatory cytokines, such as IL-10. A study indicates that lymph nodes draining UV-irradiated skin contain a population of B cells that can suppress dendritic cell function. B cell-derived IL-10 may be involved.
It is now clear that UV-induced inflammation also plays a role in the induction of immune suppressive B cells. Two important UV-induced mediators of inflammation found in the skin are platelet activating factor (PAF) and serotonin. PAF is a biologically active lipid mediator, which contributes to skin cancer development by suppressing both adaptive immunity and DNA repair. PAF and serotonin are involved in the generation of UV-activated B regulatory cells.
Natural Killer T (NKT): NKT cells can either enhance or suppress immune reactions. One of the first reports that NKT cells can have suppressive activity came from a study investigating the mechanisms responsible for UV-induced immune suppression.
Langerhans cells that migrate from the skin of UV-irradiated mice to the draining lymph nodes are essential for activating these NKT cells. The activated NKT cells secrete immunoregulatory cytokines.
Cis-urocanic acid (cis UCA): Trans-urocanic acid is found in the stratum corneum, and upon UV exposure, it isomerizes to the cis-isoform. Cis-UCA has potent immune suppressive properties. Cis-UCA mediates immune suppression by binding to the serotonin (5HT-2A) receptor.
Alarmin: Alarmins are endogenous messengers that are released following cellular damage and serve to activate innate and adaptive immune reactions to deal with infection or tissue damage. IL-33 is a alarmin, and exposing skin to UVB up-regulates IL-33. And a recent report indicates that keratinocyte-derived IL-33 depresses immune function.
Complement activation: Binding of the activated C3 fragment, iC3b to its receptor (CD11b) on monocytes results in increased IL-10 secretion with concomitant suppression in IL-12 secretion.
IL12 is an immune stimulatory cytokine. UV-induced immune suppression, the induction of T regulatory cells, and the induction of immune tolerance are all reversed by recombinant IL-12.
From the conclusion in the article: "The idea that Langerhans cells, Mast cells and NKT cells can also serve in an unconventional fashion to regulate the immune response is now well-accepted in the general immunological community; it had its first acceptance in the photoimmunological community. The realization that bioactive lipids can suppress the immune response, and the understanding of the unique role of IL-12, cis-UCA and PAF in modulating DNA repair came from studies by investigators whose focus on skin, sunlight, carcinogenesis and immune suppression equipped them to recognize unconventional roles for conventional molecules. It appears the same can be said for IL-33; its role as a mediator for UV-induced immune suppression is certainly outside the normal described function of alarmins. None of this should be too surprising. One constant of science is that once the community thinks we really understand something; new findings generally turn the existing dogma up side down.”
Perhaps the ME dogma is about to be turned up side down? Let us hope so!
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