Dataset Information

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4⁺ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

ABSTRACT: Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4⁺ T cells. Memory CD4⁺ T cells primed in high-fat diet-fed donors preferentially migrated to non-lymphoid, inflammatory sites, independent of the metabolic status of the hosts. This was due to biased CD4⁺ T cell differentiation into CD44^hi-CCR7^lo-CD62L^lo-CXCR3⁺-LFA1⁺ effector memory-like T cells upon priming in high-fat diet-fed animals. Similar phenotype was observed in obese subjects in a cohort of free-living people. This developmental bias was independent of any crosstalk between CD4⁺ T cells and dendritic cells and was mediated via direct exposure of CD4⁺ T cells to palmitate, leading to increased activation of a PI3K p110δ-Akt-dependent pathway upon priming.

SUBMITTER: Mauro C

PROVIDER: S-EPMC5355363 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

Mauro Claudio C Smith Joanne J Cucchi Danilo D Coe David D Fu Hongmei H Bonacina Fabrizia F Baragetti Andrea A Cermenati Gaia G Caruso Donatella D Mitro Nico N Catapano Alberico L AL Ammirati Enrico E Longhi Maria P MP Okkenhaug Klaus K Norata Giuseppe D GD Marelli-Berg Federica M FM

Cell metabolism 20170209 3

Low-grade systemic inflammation associated to obesity leads to cardiovascular complications, caused partly by infiltration of adipose and vascular tissue by effector T cells. The signals leading to T cell differentiation and tissue infiltration during obesity are poorly understood. We tested whether saturated fatty acid-induced metabolic stress affects differentiation and trafficking patterns of CD4+ T cells. Memory CD4+ T cells primed in high-fat diet-fed donors preferenti ...[more]

PMID: 28190771

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Project description:Chronic T cell activation and accelerated immune senescence are hallmarks of HIV infection, which may contribute to the increased risk of cardiometabolic diseases in people living with HIV (PLWH). T lymphocytes play a central role in modulating adipose tissue inflammation and, by extension, adipocyte energy storage and release. Here, we assessed the CD4+ and CD8+ T cell profiles in the subcutaneous adipose tissue (SAT) and blood of non-diabetic (n = 9; fasting blood glucose [FBG] < 100 mg/dL), pre-diabetic (n = 8; FBG = 100-125 mg/dL) and diabetic (n = 9; FBG ≥ 126 mg/dL) PLWH, in addition to non- and pre-diabetic, HIV-negative controls (n = 8). SAT was collected by liposuction and T cells were extracted by collagenase digestion. The proportion of naïve (TNai) CD45RO-CCR7+, effector memory (TEM) CD45RO+CCR7-, central memory (TCM) CD45RO+CCR7+, and effector memory revertant RA+(TEMRA) CD45RO-CCR7- CD4+ and CD8+ T cells were measured by flow cytometry. CD4+ and CD8+ TEM and TEMRA were significantly enriched in SAT of PLWH compared to blood. The proportions of SAT CD4+ and CD8+ memory subsets were similar across metabolic status categories in the PLWH, but CD4+ T cell expression of the CD69 early-activation and tissue residence marker, particularly on TEM cells, increased with progressive glucose intolerance. Use of t-distributed Stochastic Neighbor Embedding (t-SNE) identified a separate group of predominantly CD69lo TEM and TEMRA cells co-expressing CD57, CX3CR1, and GPR56, which were significantly greater in diabetics compared to non-diabetics. Expression of the CX3CR1 and GPR56 markers indicate these TEM and TEMRA cells may have anti-viral specificity. Compared to HIV-negative controls, SAT from PLWH had an increased CD8:CD4 ratio, but the distribution of CD4+ and CD8+ memory subsets was similar irrespective of HIV status. Finally, whole adipose tissue from PLWH had significantly higher expression of TLR2, TLR8, and multiple chemokines potentially relevant to immune cell homing compared to HIV-negative controls with similar glucose tolerance.

Dataset Information

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4⁺ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

Publications

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4<sup>+</sup> T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

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Dataset Information

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4+ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

Publications

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4&lt;sup&gt;+&lt;/sup&gt; T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

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OmicsDI is part of the ELIXIR infrastructure

Tweets

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4⁺ T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.

Obesity-Induced Metabolic Stress Leads to Biased Effector Memory CD4<sup>+</sup> T Cell Differentiation via PI3K p110δ-Akt-Mediated Signals.