Kidney Week

Abstract: FR-PO0155

Immune Checkpoint Molecule TIGIT Modulates Kidney T Cell Glucose Uptake and Energetics at Baseline and After AKI

Session Information

• AKI: Mechanisms - 2
  November 07, 2025 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Kapoor, Radhika, Johns Hopkins Medicine, Baltimore, Maryland, United States

Radhika Kapoor, PhD

• Patel, Shishir Kumar, Johns Hopkins Medicine, Baltimore, Maryland, United States

Shishir Kumar Patel, PhD

• Fallah Rastegar, Tara, Johns Hopkins Medicine, Baltimore, Maryland, United States

Tara Fallah Rastegar, MD

• Matsuura, Ryo, Johns Hopkins Medicine, Baltimore, Maryland, United States

Ryo Matsuura, MD, PhD, FASN

• Senoo, Nanami, Johns Hopkins Medicine, Baltimore, Maryland, United States

Nanami Senoo, PhD

• Claypool, Steven M, Johns Hopkins Medicine, Baltimore, Maryland, United States

Steven M Claypool, PhD

• Rabb, Hamid, Johns Hopkins Medicine, Baltimore, Maryland, United States

Hamid Rabb, MD, FASN

• Noel, Sanjeev, Johns Hopkins Medicine, Baltimore, Maryland, United States

Sanjeev Noel, PhD

Group or Team Name

• Hamid Rabb's Group.

Background

Prior data demonstrated increased T cell immunoreceptor with Ig and ITIM domains (TIGIT) on kidney T cells following ischemia reperfusion (IR)-AKI (Noel et al, J Am Soc Nephrol, 2023). Additionally, TIGIT knockout (KO) mice had reduced kidney IR injury and increased T cell glucose transporter 1 (GLUT1) expression compared to wild-type (WT) mice. We hypothesized that TIGIT regulates kidney T cell glucose uptake and energetics during AKI

Methods

CD3+T cells from kidneys of WT and TIGIT KO mice were cultured under normal or CoCl₂ (200µM) induced hypoxic conditions. Moreover, kidney T cells were cultured with isotype or TIGIT blocking antibody, 1G9 (25µg/ml). WT and KO mice underwent bilateral kidney IR injury to induce AKI, then CD3+ T cells were isolated 24h post IR. Glucose uptake, oxygen consumption rate (OCR), extracellular acidification rate (ECAR), maximal respiration, spare respiratory capacity (SRC), and mitochondrial ATP production were assessed

Results

TIGIT KO kidney T cells had increased glucose uptake compared to WT cells (4831±684 vs 2361±336RLU; P<0.05). Moreover, TIGIT blockade with 1G9 increased glucose uptake compared to untreated WT T cells (15148±2376 vs 4711±1390RLU; P<0.05). Under normal culture conditions, KO T cells exhibited higher basal OCR (26.2±0.03 vs 19.3±1.0pmol/min, P<0.001) and mitochondrial ATP production (83.7±6.4 vs 67.7±8.8pmol/min, P=0.06) compared to WT cells. Under chemical hypoxia, KO T cells had higher OCR (22.5±1.6 vs 16.2±0.7pmol/min, P<0.05) compared to WT cells. KO kidney T cells had higher glucose uptake at baseline (689.1±84.1 vs 262.8±25.6RLU; P<0.01) and post-IR (3478.3±479.5 vs 2002.3±324.3RLU; P<0.001) compared to WT cells. At baseline, T cells from KO mice had higher OCR (10.4±3.4 vs 4.1±0.4pmol/min, P<0.001), ECAR (1.3±0.4 vs 0.5±0.1mpH/min, P<0.01) and mitochondrial ATP production (14.2±4.5 vs 4.9±0.8pmol/min, P<0.01) compared to WT mice. Post-IR, KO T cells exhibited elevated OCR (6.34±1.8 vs 1.5±1.09pmol/min, P<0.01) and SRC (12.0±3.4 vs 3.1±1.5pmol/min, P<0.01)

Conclusion

Both TIGIT genetic deletion and antibody blockade increased glucose uptake and modulated kidney T cell bioenergetics during in vitro hypoxia and AKI. T cell metabolic reprograming via TIGIT targeting could be a potential therapeutic approach for AKI

Funding

• NIDDK Support

Digital Object Identifier (DOI)

• doi: 10.1681/ASN.2025qs6e4k0e