P36 CATHEPSIN-S INHIBITION HAS A DUAL THERAPEUTIC EFFECT ON THE SYSTEMIC AND PERIPHERAL PATHOMECHANISMS OF LUPUS NEPHRITIS

Methods: We developed novel protocols for extracting renal lymphocytes from healthy kidney tissue and diseased biopsies with and without fibrosis. Lymphocyte subsets were identified, enumerated and phenotyped by twelve-colour flow cytometry. Results: We detected significantly elevated numbers of T cells (CD45+CD3+) in diseased biopsies with interstitial fibrosis compared with healthy kidney tissue. Within this T cell compartment, numbers of T helper cells (CD3+CD4+) and cytotoxic T cells (CD3+CD8+) were elevated in fibrotic kidney tissue. Moreover, numbers of / T cells (CD3+ / +) and natural killer (NK)-T cells (CD3+CD16+) were significantly increased in fibrotic biopsies compared with diseased biopsies without fibrosis and healthy kidney tissue. Of CD3lymphoid cells, NK cells (CD3-CD56+) were elevated in fibrotic kidney tissue, in particular CD56brightCD16-/+ NK cells, the major cytokine-producing NK subtype in human peripheral tissues and secondary lymphoid organs. B cells (CD3CD19+) were also increased in fibrotic kidney tissue. Additionally, numbers of / T cells, NK-T, NK and B cells correlated with loss of kidney function (based on eGFR levels). Expression of activation molecule CD69 on renal lymphocytes was increased in fibrotic biopsies compared with healthy kidney tissue, indicative of a pathogenic phenotype. Conclusions: Collectively, our data show that lymphocyte subsets are differentially recruited into diseased human kidneys. The representation of specific lymphocyte subsets also correlates with the clinical severity of chronic kidney disease. Further identification and functional dissection of these lymphocyte subsets will enable the development of targeted treatment strategies.

• Publication year

  2016

• Venue

  Kidney International Reports

• Publication date

  2016-11-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/J.EKIR.2016.09.042
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• No references are available for this paper.

• No citing papers are available for this paper.