title: High folic acid intake reduces natural killer cell cytotoxicity in aged mice.
abstract: Presence of unmetabolized folic acid in plasma, which is indicative of folic acid intake beyond the metabolic capacity of the body, is associated with reduced natural killer (NK) cell cytotoxicity in postmenopausal women ≥50years. NK cells are cytotoxic lymphocytes that are part of the innate immune system critical for surveillance and defense against virus-infected and cancer cells. We determined if a high folic acid diet can result in reduced NK cell cytotoxicity in an aged mouse model. Female C57BL/6 mice (16-month-old) were fed an AIN-93M diet with the recommended daily allowance (1× RDA, control) or 20× RDA (high) folic acid for 3months. NK cytotoxicity was lower in splenocytes from mice fed a high folic acid diet when compared to mice on control diet (P<.04). The lower NK cell cytotoxicity in high folic acid fed mice could be due to their lower mature cytotoxic/naïve NK cell ratio (P=.03) when compared to the control mice. Splenocytes from mice on high folic acid diet produced less interleukin (IL)-10 when stimulated with lipopolysaccharide (P<.05). The difference in NK cell cytotoxicity between dietary groups was abolished when the splenocytes were supplemented with exogenous IL-10 prior to assessment of the NK cytotoxicity, suggesting that the reduced NK cell cytotoxicity of the high folic acid group was at least partially due to reduced IL-10 production. This study demonstrates a causal relationship between high folic acid intake and reduced NK cell cytotoxicity and provides some insights into the potential mechanisms behind this relationship.
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Hathairat
authors.initials: H
authors.lastname: Sawaengsri
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111; Translational Medical Center of Huaihe Clinical College, Henan University, Kaifeng, 475000, China.
authors.forename: Junpeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Christina
authors.initials: C
authors.lastname: Reginaldo
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Josiane
authors.initials: J
authors.lastname: Steluti
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Dayong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Simin Nikbin
authors.initials: SN
authors.lastname: Meydani
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111.
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.affiliation: Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111. Electronic address: Ligi.Paul_Pottenplackel@tufts.edu.
authors.forename: Ligi
authors.initials: L
authors.lastname: Paul
mesh_terms: D000375:Aging / Q000276:immunology*; D000818:Animals; D003602:Cytotoxicity, Immunologic; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D005492:Folic Acid
keywords: Folate; Folic acid; Interleukin-10; Natural killer cell cytotoxicity; immune function