Fig. 1

Vitamin D pathway and immunological activity.a Vitamin D pathway. 1—Vitamin D starting your synthesis in skin by UVB radiation; 7-dehydrol cholesterol is converted to pre vitamin D3 by UVB radiation. 2—A subsequent thermal isomerization form vitamin D3, that reaches bloodstream and binds to DBP being transported to the tissues. 3—In the liver it is metabolized to 25-hydroxyvitamin D3 by CYP2R1, 4—following another hydroxylation occurs in kidney by CYP27B1 to form 1,25 dihydroxyvitamin D3. The vitamin D levels are regulated by a feedback mechanism over CYP24A1 that hydroxylates 1,25(OH)₂D and/or 25(OH)D in position 24, generating an inactive metabolite. 5—Immune cells express CYP27B1 and CYP24A1, being able to regulate vitamin D paracrine metabolism. 6—1,25(OH)₂D binds to VDR and regulates gene expression. b Vitamin D in asthma. Asthma can be triggered by many factors such virus, allergens and air pollution; allergens frequently lead epithelial cells to release cytokines IL-25, IL-33 and TSLP, that lead to a Th2 maturation, including ILC2 activation. Th2 cells release Il-4, IL-5 and IL-13 that lead to mast cells and eosinophils recruitment and IgE production that leads to mast cell degranulation and amplification of inflammation. IL-13 leads to increase mucus production in epithelium. The inflammatory cell infiltration leads smooth muscle thickening and contraction; reduction of airway lumen culminates to induce asthma symptoms. A non Th2 asthma profile, can be trigged by virus and air Pollutants, and lead to a Th1 or Th17 response, of neutrophilic profile. T reg cells reduce Th1, Th2 and Th17 response controlling inflammation. 1,25(OH)D can inhibit ILC2, eosinophilic and mast cell proliferation; Inhibits IL-4 release and IgE synthesis. 1.25(OH)D induces Treg response. Orange arrow—activation. Blue arrow—inhibition. TSLP thymic stromal lymphoprotein