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W178 - Single-cell Transcriptomic Characterization Reveals Changes in MAIT and Regulatory T Cells with Advancing Age in a Diverse American Population

Wednesday, June 21, 2023

7:30 AM – 7:30 PM

Hanane Touil – Post-Doc, Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Masashi Fujita – Neurology – Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Pallavi Gaur – Neurology – Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Adam Brickman – Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA; Vilas Menon – 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA; Yaakov Stern – Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, New York, USA.; Philip De Jager – 1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA. Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA

HT

Hanane Touil, Ph.D.

postdoctoral fellow
1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
New York, New York, United States
HT

Hanane Touil, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
MF

Masashi Fujita, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
PG

Pallavi Gaur, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
AB

Adam Brickman, PhD

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA
VM

Vilas Menon, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
YS

Yaakov Stern, PhD

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, New York, USA.
PD

Philip De Jager, MD, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA. Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA
HT

Hanane Touil, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
MF

Masashi Fujita, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
PG

Pallavi Gaur, PhD

Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
AB

Adam Brickman, PhD

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, USA
VM

Vilas Menon, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA
YS

Yaakov Stern, PhD

Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, New York, USA.
PD

Philip De Jager, MD, PhD

1Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, USA. Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, USA

Abstract Text: Immunosenescence (ISC) is the natural aging of the immune system that consists in gradual age-related changes within immune-cell composition and function. Age-associated cellular phenotypic changes are well-established, yet few studies extensively characterized the transcriptomic profile of ethnically diverse populations. Here, we assessed transcriptomic and proteomic profiles in a large-scale manner (n=200, age: 25-88 years), using single cell-RNA-sequencing and CITE-Seq.

We identified 31 distinct PBMCs cell-clusters associated with age after adjusting for sex and technical covariates; including established age-related populations such as Naïve CD8+ (p=6.35x10-23) and CD4+ (p=1.0x10-9) and NK-cell subsets (p=0.0007). However, unbiased clustering revealed new age-associated immune-cell subset changes, namely cytotoxic CD4+ CTLT-cells (p=0.009), mucosal associated invariant T-cells (MAIT) (p=0.0013), regulatory T-cells (p=0.006) and -T-cells (p=9.51x10-5). The MAIT cluster is subdivided into three subtypes, all of which decrease with age. We report reciprocal ISC trajectory changes within the MAIT and regulatory T-cell compartments, supporting a favorable tumor environment. These data are then used to calculate an immunologic age that is enhanced compared to our cytometry-derived estimates.

Our data offer a new level of resolution of peripheral blood immunosenescence across diverse populations. While certain associations with genetic ancestry are seen, they’re not related to those cellular populations influenced by advancing age. These data enabled us to identify more cell-subtypes that inform the immunologic age calculation, and further produced accurate estimates improving personalized therapeutic strategies that harness the immune system. The reciprocal MAIT and regulatory T-cell trajectories also shint at dysfunction that may contribute to higher cancer incidence in older individuals.