Loss of solute carriers in T cell-mediated rejection in mouse and human kidneys: an active epithelial injury-repair response.
T cell-mediated rejection of kidney allografts causes epithelial deterioration, manifested by tubulitis, but the mechanism remains unclear. We hypothesized that interstitial inflammation triggers a stereotyped epithelial response similar to that triggered by other types of injury such as ischemia-reperfusion. We identified solute carrier transcripts with decreased expression in mouse allografts, and compared their behavior in T cell-mediated rejection to native kidneys with ischemic acute tubular necrosis (ATN). Average loss of solute carrier expression was similar in ATN (77%) and T cell-mediated rejection (75%) with high correlation of individual transcripts. Immunostaining of SLC6A19 confirmed loss of proteins. Analysis of human kidney transplant biopsies confirmed that T cell-mediated rejection and ATN showed similar loss of solute carrier mRNAs. The loss of solute carrier expression was weakly correlated with interstitial inflammation, but kidneys with ATN showed decreased solute carriers despite minimal inflammation. Loss of renal function correlated better with decreased solute carrier expression than with histologic lesions (r = 0.396, p < 0.001). Thus the loss of epithelial transcripts in rejection is not a unique consequence of T cell-mediated rejection but an active injury-repair response of epithelium, triggered by rejection but also by other injury mechanisms.
Einecke
G
G
Department of Nephrology, Hannover Medical School, Hanover, Germany.
Kayser
D
D
Vanslambrouck
J M
JM
Sis
B
B
Reeve
J
J
Mengel
M
M
Famulski
K S
KS
Bailey
C G
CG
Rasko
J E J
JE
Halloran
P F
PF
D026921:Amino Acid Transport Systems, Neutral / Q000096:biosynthesis / Q000378:metabolism; D000818:Animals; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology; D007683:Kidney Tubular Necrosis, Acute / Q000378:metabolism / Q000473:pathology*; D007684:Kidney Tubules / Q000473:pathology; D026901:Membrane Transport Proteins / Q000502:physiology*; D051379:Mice; D008808:Mice, Inbred CBA; D014945:Wound Healing / Q000276:immunology
D026921:Amino Acid Transport Systems, Neutral; D026901:Membrane Transport Proteins; C505021:SLC6A19 protein, mouse