Back to all available

Aging-related CD8⁺ T cell alterations and CAMK1D activation in the pathogenesis of diabetic kidney disease

molecular-biology
geriatrics
immunology
nephrology
medical-genetics

Abstract

Background. Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), accelerating age-related decline in eGFR, leading to a markedly increased prevalence of DKD among elderly diabetic patients. Recent studies suggest that immune dysregulation plays a pivotal role in DKD progression; however, the cellular and molecular mechanisms linking aging, immune infiltration, and DKD remain unclear.

Methods. We used single-cell RNA sequencing (scRNA-seq) analysis to characterize immune cell dynamics between the young, the elderly, and DKD patients. Based on the scRNA-seq analysis, Mendelian randomization (MR) analysis of differentially expressed genes (DEGs) in CD8+ T cells was conducted to explore the causal relationship between DEGs and DKD.

Results. We observed CD8⁺ T cell cluster was the most abundant T cell type. However, the proportion of CD8⁺ T cell clusters within the T cell compartment showed a decreasing trend from young individuals to elderly individuals and DKD patients. MR analysis of DEGs in CD8⁺ T cells identified CAMK1D as exhibiting the strongest causal relationship with DKD. CAMK1D was upregulated in DKD kidney tissues, and its expression was localized to CD8⁺ T cells, as confirmed by immunofluorescence staining. Functional analysis revealed that CAMK1D⁺ CD8⁺ T cells engaged in pro-inflammatory and pro-fibrotic signaling with various renal cell types and showed enrichment in metabolic pathways implicated in DKD.

Conclusion. Our results highlighted the important role of CD8⁺ T cells in shaping the renal immune microenvironment in both DKD and aging. CAMK1D may serve as a shared molecular risk factor linking aging and diabetic renal injury.

Ask to review this manuscript

Notes for potential reviewers

  • Volunteering is not a guarantee that you will be asked to review. There are many reasons: reviewers must be qualified, there should be no conflicts of interest, a minimum of two reviewers have already accepted an invitation, etc.
  • This is NOT OPEN peer review. The review is single-blind, and all recommendations are sent privately to the Academic Editor handling the manuscript. All reviews are published and reviewers can choose to sign their reviews.
  • What happens after volunteering? It may be a few days before you receive an invitation to review with further instructions. You will need to accept the invitation to then become an official referee for the manuscript. If you do not receive an invitation it is for one of many possible reasons as noted above.
  • PeerJ does not judge submissions based on subjective measures such as novelty, impact or degree of advance. Effectively, reviewers are asked to comment on whether or not the submission is scientifically and technically sound and therefore deserves to join the scientific literature. Our Peer Review criteria can be found on the "Editorial Criteria" page - reviewers are specifically asked to comment on 3 broad areas: "Basic Reporting", "Experimental Design" and "Validity of the Findings".
  • Reviewers are expected to comment in a timely, professional, and constructive manner.
  • Until the article is published, reviewers must regard all information relating to the submission as strictly confidential.
  • When submitting a review, reviewers are given the option to "sign" their review (i.e. to associate their name with their comments). Otherwise, all review comments remain anonymous.
  • All reviews of published articles are published. This includes manuscript files, peer review comments, author rebuttals and revised materials.
  • Each time a decision is made by the Academic Editor, each reviewer will receive a copy of the Decision Letter (which will include the comments of all reviewers).

If you have any questions about submitting your review, please email us at [email protected].