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Abstract: FR-PO250

Turning the Kidney Into a Lymphoid Organ

Session Information

Category: Genetic Diseases of the Kidneys

  • 1101 Genetic Diseases of the Kidneys: Cystic


  • Atwood, Daniel, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Oto, Ozgur Akin, Istanbul Universitesi Istanbul Tip Fakultesi, Istanbul, Istanbul, Turkey
  • Chaudhary, Anjana, University of Colorado Denver School of Medicine, Aurora, Colorado, United States
  • Edelstein, Charles L., University of Colorado Denver School of Medicine, Aurora, Colorado, United States

Pkd1RC/RC mice (RC), a hypomorphic Pkd1 mouse model of ADPKD, have suppressed kidney autophagy (Atwood, Edelstein et al. Cell Signal. 2020). We hypothesized that knocking out autophagy (ATG7) in the kidney in aged mice would induce cyst growth. The first aim of the study was to breed kidney-specific autophagy knockout (ATG7-/-) mice.


ATG7-/- mice were generated using a renal tubule specific cadherin Cre-Lox system. IHC was done with the VectaStain ABC kit. Staining quantitation was done using macros on the Aperio Imagescope. TLT #, size, and index was obtained from H&E sections using an NIS Element macro.


400d ATG7-/- mice had no cysts and normal kidney function. Surprisingly, large tertiary lymphoid tissues (TLT)(up to 9%) of the area of the kidney were seen in ATG7-/- kidneys. There was increased TLT size, number, and index in ATG7-/- vs. WT (Table). TLTs are ectopic lymphoid tissues composed of lymphocyte aggregates that develop de novo in nonlymphoid organs. TLTs form after tissue injury, infection, or chronic inflammation in various kidney diseases. The phenotype of TLTs in ATG7-/- was confirmed by the presence of T cell(CD3, 4, and 8), and B cell(CXCL13, CD21) markers and intense proliferation(PCNA) in the TLTs. There was also large amount of staining for pS6(mTORC1), an inducer of proliferation, in the TLTs. PKD kidneys have chronic inflammation which is known to promote the formation of TLTs. There was increased number, size, and index of TLTs in kidneys from RC mice(Table). There was intense proliferation of T cells and increased pS6 (mTORC1) staining in the TLTs in RC kidneys. Treating RC mice with the mTOR inhibitor Torin2(10 mg/kg IP) from 50-120d virtually eliminated TLTs.


The following novel findings are described: The presence of numerous, large and discrete TLTs in aged tubule-specific ATG7-/- kidneys, intense pS6 (mTORC1) in TLTs in ATG7-/- kidneys, first description of the presence of TLTs in PKD kidneys, and virtual elimination of TLTs by treatment of RC mice with an mTOR inhibitor. These data suggest a previously undescribed relationship between suppressed autophagy, activation of mTORC1 and the formation and growth of TLTs.

 WT 120dRC 120dRC+Torin2 120dWT 400dATG7-/- 400dRC 400d
TLT #04.8***0.3**3.012.4**12.8
Avg TLT size (mm2)00.014***0.002**0.0430.096**0.057*
TLT Index (% of kidney)00.21***0.01**0.363.09**1.71

*P>0.05 **P>0.01 ***P>0.001


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