29 research outputs found
The effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell death
Dietary n-3 polyunsaturated fatty acids (PUFA) have been shown to potently attenuate T cell-mediated inflammation, in part, by suppressing T cell activation and proliferation. Apoptosis is an important mechanism for preventing chronic inflammation by maintaining T cell homeostasis through the contraction of populations of activated T cells. We hypothesized that dietary n-3 PUFA would promote T cell apoptosis, thus, providing an additional mechanism to explain the anti-inflammatory effects. We specifically examined activation-induced cell death (AICD) since it is the form of apoptosis associated with peripheral T cell deletion involved in immunological tolerance and T cell homeostasis. Female C57BL/6 mice were fed diets containing either n-6 PUFA (control) or n-3 PUFA for 14 d. Splenic T cells were stimulated with CD3/CD28, CD3/PMA, or PMA/Ionomycin for 48 h followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide and flow cytometry. Cytokine analyses revealed that n-3 PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile (high IFN, low IL-4) compared to mice fed the n-6 PUFA control diet. Dietary n-3 PUFA significantly altered the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in T cell membranes.
To examine the apparently selective effect of dietary n-3 PUFA on AICD in Th1 cells, CD4+ T cells were polarized in vitro to a Th1 phenotype by culture with IL-4, IL-2, and IL-12 for 2 d, followed by culture with IL-2 and IL-12 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids. Following polarization and reactivation, we observed that n-3 PUFA enhanced Th1 polarization and AICD only in cells cultured in the presence of MS, but not in fetal bovine serum. The n-3 PUFA enhancement of Th1 polarization and AICD was associated with the maintenance of diet-induced changes in EPA (20:5n-3) and DHA (22:6n-3) in plasma T cell membrane lipid rafts. Overall, these results suggest that dietary n-3 PUFA enhance both the polarization and deletion of pro-inflammatory Th1 cells, possibly as a result of alterations in lipid raft fatty acid composition
The effect of dietary n-3 polyunsaturated fatty acids on T cell subset activation-induced cell death
Dietary n-3 polyunsaturated fatty acids (PUFA) have been shown to potently attenuate T cell-mediated inflammation, in part, by suppressing T cell activation and proliferation. Apoptosis is an important mechanism for preventing chronic inflammation by maintaining T cell homeostasis through the contraction of populations of activated T cells. We hypothesized that dietary n-3 PUFA would promote T cell apoptosis, thus, providing an additional mechanism to explain the anti-inflammatory effects. We specifically examined activation-induced cell death (AICD) since it is the form of apoptosis associated with peripheral T cell deletion involved in immunological tolerance and T cell homeostasis. Female C57BL/6 mice were fed diets containing either n-6 PUFA (control) or n-3 PUFA for 14 d. Splenic T cells were stimulated with CD3/CD28, CD3/PMA, or PMA/Ionomycin for 48 h followed by reactivation with the same stimuli for 5 h. Apoptosis was measured using Annexin V/propidium iodide and flow cytometry. Cytokine analyses revealed that n-3 PUFA enhanced AICD only in T cells expressing a Th1-like cytokine profile (high IFN, low IL-4) compared to mice fed the n-6 PUFA control diet. Dietary n-3 PUFA significantly altered the fatty acid composition of phosphatidylcholine and phosphatidylethanolamine in T cell membranes.
To examine the apparently selective effect of dietary n-3 PUFA on AICD in Th1 cells, CD4+ T cells were polarized in vitro to a Th1 phenotype by culture with IL-4, IL-2, and IL-12 for 2 d, followed by culture with IL-2 and IL-12 for 3 d in the presence of diet-matched homologous mouse serum (MS) to prevent loss of cell membrane fatty acids. Following polarization and reactivation, we observed that n-3 PUFA enhanced Th1 polarization and AICD only in cells cultured in the presence of MS, but not in fetal bovine serum. The n-3 PUFA enhancement of Th1 polarization and AICD was associated with the maintenance of diet-induced changes in EPA (20:5n-3) and DHA (22:6n-3) in plasma T cell membrane lipid rafts. Overall, these results suggest that dietary n-3 PUFA enhance both the polarization and deletion of pro-inflammatory Th1 cells, possibly as a result of alterations in lipid raft fatty acid composition
Variants in autophagy-related genes and clinical characteristics in melanoma: a population-based study
Autophagy has been linked with melanoma risk and survival, but no polymorphisms in autophagy-related (ATG) genes have been investigated in relation to melanoma progression. We examined five single-nucleotide polymorphisms (SNPs) in three ATG genes (ATG5; ATG10; and ATG16L) with known or suspected impact on autophagic flux in an international population-based case-control study of melanoma. DNA from 911 melanoma patients was genotyped. An association was identified between (GG) (rs2241880) and earlier stage at diagnosis (OR 0.47; 95% Confidence Intervals (CI) = 0.27-0.81, P = 0.02) and a decrease in Breslow thickness (P = 0.03). The ATG16L heterozygous genotype (AG) (rs2241880) was associated with younger age at diagnosis (P = 0.02). Two SNPs in ATG5 were found to be associated with increased stage (rs2245214 CG, OR 1.47; 95% CI = 1.11-1.94, P = 0.03; rs510432 CC, OR 1.84; 95% CI = 1.12-3.02, P = 0.05). Finally, we identified inverse associations between ATG5 (GG rs2245214) and melanomas on the scalp or neck (OR 0.20, 95% CI = 0.05-0.86, P = 0.03); ATG10 (CC) (rs1864182) and brisk tumor infiltrating lymphocytes (TILs) (OR 0.42; 95% CI = 0.21-0.88, P = 0.02), and ATG5 (CC) (rs510432) with nonbrisk TILs (OR 0.55; 95% CI = 0.34-0.87, P = 0.01). Our data suggest that ATG SNPs might be differentially associated with specific host and tumor characteristics including age at diagnosis, TILs, and stage. These associations may be critical to understanding the role of autophagy in cancer, and further investigation will help characterize the contribution of these variants to melanoma progression
The Atacama Cosmology Telescope: DR6 Gravitational Lensing Map and Cosmological Parameters
We present cosmological constraints from a gravitational lensing mass map
covering 9400 sq. deg. reconstructed from CMB measurements made by the Atacama
Cosmology Telescope (ACT) from 2017 to 2021. In combination with BAO
measurements (from SDSS and 6dF), we obtain the amplitude of matter
fluctuations at 1.8% precision,
and the Hubble
constant at
1.6% precision. A joint constraint with CMB lensing measured by the Planck
satellite yields even more precise values: ,
and . These measurements agree
well with CDM-model extrapolations from the CMB anisotropies measured
by Planck. To compare these constraints to those from the KiDS, DES, and HSC
galaxy surveys, we revisit those data sets with a uniform set of assumptions,
and find from all three surveys are lower than that from ACT+Planck
lensing by varying levels ranging from 1.7-2.1. These results motivate
further measurements and comparison, not just between the CMB anisotropies and
galaxy lensing, but also between CMB lensing probing on
mostly-linear scales and galaxy lensing at on smaller scales. We
combine our CMB lensing measurements with CMB anisotropies to constrain
extensions of CDM, limiting the sum of the neutrino masses to eV (95% c.l.), for example. Our results provide independent
confirmation that the universe is spatially flat, conforms with general
relativity, and is described remarkably well by the CDM model, while
paving a promising path for neutrino physics with gravitational lensing from
upcoming ground-based CMB surveys.Comment: 30 pages, 16 figures, prepared for submission to ApJ. Cosmological
likelihood data is here:
https://lambda.gsfc.nasa.gov/product/act/actadv_prod_table.html ; likelihood
software is here: https://github.com/ACTCollaboration/act_dr6_lenslike . Also
see companion papers Qu et al and MacCrann et al. Mass maps will be released
when papers are publishe
The Atacama Cosmology Telescope: DR6 gravitational lensing map and cosmological parameters
We present cosmological constraints from a gravitational lensing mass map covering 9400 deg2 reconstructed from measurements of the cosmic microwave background (CMB) made by the Atacama Cosmology Telescope (ACT) from 2017 to 2021. In combination with measurements of baryon acoustic oscillations and big bang nucleosynthesis, we obtain the clustering amplitude Ï 8 = 0.819 ± 0.015 at 1.8% precision, S8âĄÏ8(Ωm/0.3)0.5=0.840±0.028 , and the Hubble constant H 0 = (68.3 ± 1.1) km sâ1 Mpcâ1 at 1.6% precision. A joint constraint with Planck CMB lensing yields Ï 8 = 0.812 ± 0.013, S8âĄÏ8(Ωm/0.3)0.5=0.831±0.023 , and H 0 = (68.1 ± 1.0) km sâ1 Mpcâ1. These measurements agree with ÎCDM extrapolations from the CMB anisotropies measured by Planck. We revisit constraints from the KiDS, DES, and HSC galaxy surveys with a uniform set of assumptions and find that S 8 from all three are lower than that from ACT+Planck lensing by levels ranging from 1.7Ï to 2.1Ï. This motivates further measurements and comparison, not just between the CMB anisotropies and galaxy lensing but also between CMB lensing probing z ⌠0.5â5 on mostly linear scales and galaxy lensing at z ⌠0.5 on smaller scales. We combine with CMB anisotropies to constrain extensions of ÎCDM, limiting neutrino masses to âm Îœ < 0.13 eV (95% c.l.), for example. We describe the mass map and related data products that will enable a wide array of cross-correlation science. Our results provide independent confirmation that the universe is spatially flat, conforms with general relativity, and is described remarkably well by the ÎCDM model, while paving a promising path for neutrino physics with lensing from upcoming ground-based CMB surveys