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1.
Nat Immunol ; 24(7): 1124-1137, 2023 07.
Article in English | MEDLINE | ID: mdl-37217705

ABSTRACT

The magnitude and quality of the germinal center (GC) response decline with age, resulting in poor vaccine-induced immunity in older individuals. A functional GC requires the co-ordination of multiple cell types across time and space, in particular across its two functionally distinct compartments: the light and dark zones. In aged mice, there is CXCR4-mediated mislocalization of T follicular helper (TFH) cells to the dark zone and a compressed network of follicular dendritic cells (FDCs) in the light zone. Here we show that TFH cell localization is critical for the quality of the antibody response and for the expansion of the FDC network upon immunization. The smaller GC and compressed FDC network in aged mice were corrected by provision of TFH cells that colocalize with FDCs using CXCR5. This demonstrates that the age-dependent defects in the GC response are reversible and shows that TFH cells support stromal cell responses to vaccines.


Subject(s)
T-Lymphocytes, Helper-Inducer , Vaccines , Animals , Mice , B-Lymphocytes , T Follicular Helper Cells , Germinal Center , Aging
2.
Obes Surg ; 26(6): 1237-46, 2016 06.
Article in English | MEDLINE | ID: mdl-26328533

ABSTRACT

BACKGROUND: Although patients experience hair loss and dry skin which may be attributable to deficiency in essential fatty acids (EFAs), the impact of bariatric surgeries on EFA status is unknown. METHODS: This study aimed to assess plasma phospholipid fatty acid profiles following adjustable gastric banding (AGB), which restricts dietary fat intake, versus Roux-en-Y gastric bypass (RYGB), which also promotes fat malabsorption. Serial measures were obtained before and 1 and 6 months from women undergoing RYGB (N = 13) and AGB (N = 5). Measures included the composition of plasma fatty acids in phospholipids, dietary intake, and body fat mass. Friedman and Mann-Whitney tests were used to assess differences over time and between groups, respectively, p < 0.05. RESULTS: Dietary intake of fats decreased equally at 1 and 6 months following RYGB and AGB. By 6 months, the RYGB group lost more body fat. There were no remarkable changes in EFA in plasma phospholipids following AGB. However, following RYGB, a transient increase in 20:4N6 (+18 %) and a decrease in 20:3N6 at 1 (-47 %) and 6 months (-47 %) were observed. Similar changes were observed in N3 fatty acids following RYGB, including a transient increase in 22:6N3 (+11 %) and decreases in 20:5N3 (-79 and -67 % at 1 and 6 months, respectively). EFA status improved following surgery in the RYGB group. CONCLUSIONS: We demonstrate alterations in plasma EFA following RYGB. The status of EFA improved, but the decrease in 20:5N3, the precursor for anti-inflammatory eicosanoids, may be a concern.


Subject(s)
Fatty Acids, Essential/blood , Gastric Bypass/adverse effects , Gastroplasty/adverse effects , Obesity, Morbid/surgery , Adiposity , Adult , Diet , Dietary Fats/administration & dosage , Energy Intake , Fatty Acids, Essential/deficiency , Female , Gastric Bypass/methods , Gastroplasty/methods , Humans , Middle Aged , Obesity, Morbid/blood , Phospholipids/blood , Postoperative Period , Young Adult
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