Sunlight and its effects
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"The mechanisms driving local and systemic UV immune suppression are different. Although much is known about how UV suppresses local cutaneous immune responses, the mechanisms by which UV suppresses distant immunity are only just being revealed. Our study has shown for the first time, to our knowledge, that UV exposure of the skin systemically alters T cell recirculation, preferentially trapping naive and, to a lesser extent, central memory T cells in the UV-exposed skin-draining lymph nodes. This cellular sequestration away from peripheral blood was the result of a UV-triggered increase in SphK activity, leading to elevated levels of S1P in regional lymph nodes. This increase in S1P in turn caused a downregulation of S1P1 expression on T cells leading to their sequestration."
"Pharmacological interference with normal lymphocyte trafficking is a highly effective way to induce therapeutic immune suppression. Natalizumab for example, is an mAb that prevents leukocyte trans-migration by blocking α4β1 integrin leukocyte adhesion to endothelial VCAM-1 (54). Another example is fingolimod, a functional S1P receptor agonist that induces the internalization and downregulation of S1P1, the functional result of which is a reduction in circulating leukocytes (35), in particular naive and central memory T cells (34), and an accumulation of T cells within lymph nodes (36). Interference with normal lymphocyte trafficking following administration of natalizumab and fingolimod causes profound systemic immune suppression that is effective in the treatment of autoimmune diseases, particularly MS (55, 56). We have shown in this study that exposure to UV, which is a known immune suppressant and associated with protection from MS (4), also interferes with normal lymphocyte trafficking."
"The ability of UV to alter T cell recirculation, promote the expansion of UV-activated Tregs (18), and inhibit T cell proliferation upon stimulation (16) provides a potent formula for the comprehensive suppression of cell-mediated immunity. The trapping of naive T cells in the skin-draining lymph nodes maximizes the chance of interactions with other cellular mediators of UV-induced immune suppression, such as dendritic cells (63), mast cells (37), B cells (50, 64), and UV-Tregs (19). It is known that if an Ag is presented during the first 24–72 h of exposure to UV, T cell activation is suppressed (16) in part by UV-Treg and B cell production of IL-10 (19, 20, 65). We have now shown that even if activation of naive T cells occurs, UV not only limits clonal expansion (16), but it also interferes with normal lymphocyte recirculation by reducing the likelihood of cells exiting the lymph nodes."
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@Amazoniac, Super interesting. Thanks for the find.
Inspired me to learn a bit about S1P.
- The sphingosine-1-phosphate (S1P) is very important for immune suppression and cell proliferation via its receptor 1 (S1PR1) :
"..S1PR1 is crucial for S1P-induced cell migration and suggested that S1PR1 is a master regulator of cell movement", as was shown in this work."
How clever: UVR modulates the systemic immune system via this global mechanism (S1PR1) and not via vitamin D (8) or urocanic acid (26), which I reckon would be more indirect solutions than the S1PR1 one.
[Reference number 8 and 26 are taken the paper in the OP.] - The sphingosine-1-phosphate (S1P) is very important for immune suppression and cell proliferation via its receptor 1 (S1PR1) :
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Digging a bit deeper into refs 8 and 26 in my post above.
(8) UV radiation suppresses experimental autoimmune encephalomyelitis independent of vitamin D production
by Bryan R Becklund , Kyle S Severson, Souriya V Vang, Hector F DeLucaFrom the abstract:
Our results indicate that continuous treatment with UVR dramatically suppresses clinical signs of [the experimental autoimmune encephalomyelitis] EAE. Interestingly, disease suppression occurs with only a modest, transient increase in serum 25(OH)D(3) levels. Further analysis demonstrated that the levels of 25(OH)D(3) obtained upon UVR treatment were insufficient to suppress EAE independent of UVR treatment. These results suggest that UVR is likely suppressing disease independent of vitamin D production, and that vitamin D supplementation alone may not replace the ability of sunlight to reduce MS susceptibility.
(26) Suppression of experimental autoimmune encephalomyelitis by ultraviolet light is not mediated by isomerization of urocanic acid
by Amy A. Irving, Steven J. Marling, Lori A. Plum, and Hector F. DeLucaFrom the Discussion:
It is clear that ultraviolet B exposure efficiently prevents EAE, though we find no evidence to support [urocanic acid] UCA isomerization as the mediator of this suppression. This is not the first study to discount UCA as a mediator of UV immunosuppression, or that UCA administration does not mimic the effects of UV exposure.
