title: Lymphocytes promote albuminuria, but not renal dysfunction or histological damage in a mouse model of diabetic renal injury.
abstract: OBJECTIVE
  Diabetic nephropathy is an inflammatory disease with prominent leucocyte infiltration of the kidneys. While the importance of macrophages in diabetic renal injury has been clearly demonstrated, the role of lymphocytes is still unknown. We therefore examined the development of diabetic renal injury in lymphocyte-deficient mice.
  
  
  METHODS
  Streptozotocin was used to induce diabetes in Rag1(-/-) mice, which lack mature T and B lymphocytes, and in wild-type (Rag1(+/+) ) controls. The development of renal injury was examined over 20 weeks of diabetes.
  
  
  RESULTS
  Both groups developed equivalent diabetes, however only Rag1(+/+) mice had kidney infiltration with CD4, CD8, CD22 and forkhead box P3-positive cells, as well as glomerular immunoglobulin deposition. At 20 weeks, Rag1(+/+) mice exhibited renal hypertrophy, increased mesangial and interstitial matrix, kidney macrophage accumulation, tubular injury, progressive albuminuria and a decline in renal function. In comparison, diabetic Rag1(-/-) mice showed similar histological damage, matrix expansion, macrophage accrual and loss of renal function, but were protected from increasing albuminuria. This protection was associated with protection against loss of podocytes and glomerular podocin production, and with reduced glomerular macrophage activation.
  
  
  CONCLUSIONS
  These results show that lymphocytes contribute to the development of diabetic albuminuria, which may partly arise from increasing glomerular macrophage activation and podocyte damage. In contrast, lymphocytes do not appear to promote tubular injury, increased matrix deposition or decline in renal function in a mouse model of type 1 diabetes. Our findings suggest that innate immunity rather than adaptive immune responses are the major inflammatory contributor to the progression of diabetic renal injury.
authors.affiliation: Department of Nephrology, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168, Australia.
authors.forename: A K H
authors.initials: AK
authors.lastname: Lim
authors.forename: F Y
authors.initials: FY
authors.lastname: Ma
authors.forename: D J
authors.initials: DJ
authors.lastname: Nikolic-Paterson
authors.forename: A R
authors.initials: AR
authors.lastname: Kitching
authors.forename: M C
authors.initials: MC
authors.lastname: Thomas
authors.forename: G H
authors.initials: GH
authors.lastname: Tesch
mesh_terms: D000419:Albuminuria / Q000209:etiology* / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001786:Blood Glucose; D003921:Diabetes Mellitus, Experimental / Q000276:immunology / Q000473:pathology; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000276:immunology / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D007113:Immunity, Innate / Q000276:immunology; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D008214:Lymphocytes / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose