Journal
CLINICAL AND EXPERIMENTAL IMMUNOLOGY
Volume 197, Issue 2, Pages 205-213Publisher
WILEY
DOI: 10.1111/cei.13344
Keywords
ageing; inflammation; senescent; T cell; type 2 diabetes
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Funding
- British Heart Foundation
- Academy of Medical Science
- Wellcome trust
- Rosetrees Trust
- CRUK Flow Cytometry Core Service at Barts Cancer Institute [C16420/A18066]
- British Oxygen Company Research Chair in Anaesthesia
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Type 2 diabetes is a global health priority, given that it is driven, in part, by an ageing population, the role of immune senescence has been overlooked. This is surprising, as the functional impairments of senescent T cells show strong similarities to patients with hyperglycaemia. Immune senescence is typified by alterations in T cell memory, such as the accumulation of highly differentiated end-stage memory T cells, as well as a constitutive low-grade inflammation, which drives further immune differentiation. We show here in a preliminary study that people living with type 2 diabetes have a higher circulating volume of senescent T cells accompanied with a higher level of systemic inflammation. This inflammatory environment drives the expression of a unique array of chemokine receptors on senescent T cells, most notably C-X-C motif chemokine receptor type 2. However, this increased expression of migratory markers does not translate to improved extravasation owing to a lack of glucose uptake by the T cells. Our results therefore demonstrate that the presence of senescent T cells has a detrimental impact on immune function during type 2 diabetes.
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