P1608CXCL13 IS STRONGLY INDUCED BY RENAL ISCHEMIA REPERFUSION INJURY AND CORRELATES WITH SEVERITY OF RENAL INFLAMMATION

Background and Aims Ischemia reperfusion injury (IRI) is a strong trigger of inflammation and is tightly linked to renal allograft damage and function. CXCL13 or B lymphocyte chemoattractant (BLC) is a chemokine that controls B cell organization in lymphoid tissues and has recently been described as a biomarker for B cell involvement in acute kidney allograft rejection. Method To show, that CXCL13 is already induced by IRI alone we used renal IRI models in mice with different ischemia times and a kidney transplantation model. We measured serum CXCL13 and characterized cell infiltrates by immunohistochemistry and performed single cell RNA sequencing. Allogenic and isogenic kidney transplantation (KTX) in mice was done to evaluate these findings in the transplant setting. Results Systemic CXCL13 levels increased within hours after surgery in a time dependent manner, both after induction of IRI and KTX. Levels of CXCL13 increased with duration of ischemia time and were higher in allogenic than isogenic transplantation with equal duration of ischemia. CXCR5, the receptor for CXCL13, is mainly expressed on B lymphocytes but also on a subset of T lymphocytes and macrophages. CXCR5 positive infiltrates were detected in IRI kidneys seven days after injury. In kidney allografts interstitial B cell infiltrates were observed as early as seven days and increased further towards three weeks after KTX. Conclusion The current findings indicate that IRI is a strong trigger of CXCL13 expression in the kidney and release into the circulation, which is followed by B lymphocyte infiltration into damaged tissue in ischemic and renal allografts.