As a direct result of UVR, several immunosuppressive factors are produced. These include cis-UCA; vitamin D; platelet-activating factor receptor (PAF-R) agonists and platelet-like ligands; and AhR ligands such as FICZ. These factors cause the release of cytokines such as histamine, prostaglandin E₂ (PGE₂), TNF, and IL-10 (198) and IL-33 (199) from mast cells and keratinocytes and influence the differentiation of CD4⁺ T cells to an immunosuppressive phenotype. Vitamin D influences the differentiation of monocytes to macrophages and DCs by downregulating the vitamin D receptor, resulting in decreased DC maturation; and by downregulating costimulatory molecules, thus reducing antigen-presenting ability. Vitamin D is also reported to influence immunosuppression via keratinocytes, Tregs, and mast cells. Cis-UCA has potent immunosuppressive effects mediated through numerous dermal cells via the serotonin receptor on, but not limited to, mast cells and keratinocytes. Cis-UCA interacts with dermal mast cells to frequently induce degranulation of both histamine and PGE₂. Cis-UCA is able to stimulate the release of TNF-α from keratinocytes, preventing Langerhans cells from migrating to lymph nodes and presenting antigen to T cells; as well as to stimulate production of PGE₂. UV-mediated damage to keratinocytes produces PAFs to also release PGE₂, as well as IL-10 and TNF. Absorption of UVB by tryptophan produces AhR ligands, including FICZ and TCDD, that signal through keratinocytes and T cells. AhR ligands upregulate COX-2 in keratinocytes, resulting in increased production of PGE₂, which influences the recruitment of Tregs. AhR ligands also influence T cells via adaptive and regulatory-like T cells (induced Tregs and Tr1 cells). AhR ligands enhance the production of IL-10 from naive CD4⁺ T cells. AhR ligands along with TGF-β are also able to induce suppressive T cell phenotypes via the upregulation of FOXP3 either via Smad1 or potentially via direct binding of AhR to the FOXP3 promoter.