Targeted delivery of IL-21 neutralizing nanotherapeutics to lymph nodes and kidney allografts attenuates B cell alloimmunity.

IF 14.8 1区医学 Q1 UROLOGY & NEPHROLOGY

Kidney international Pub Date : 2025-04-21 DOI:10.1016/j.kint.2025.03.017

Hengcheng Zhang,Gianmarco Sabiu,Sungwook Jung,Manuel A Podestà,Jing Zhao,Maya Gempler,Minako Yamamura,Jinxu Miao,George C Tsokos,Ahmad Karadagi,Tatsuo Kawai,Reza Abdi,Peter T Sage

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Abstract

INTRODUCTION Antibody-mediated rejection (ABMR) after allogeneic kidney transplantation is a substantial clinical problem for which there are no specific treatments. High endothelial venules (HEV) are specialized veins which are normally present only in lymph nodes (LN) facilitating immune cell entry. Here, we show that kidneys undergoing rejection develop HEV-like structures derived from host cells. METHODS We developed a nano-delivery system targeting HEVs to simultaneously deliver therapeutics to draining LN and kidney allografts. RESULTS Using this system, we preferentially delivered IL-21 neutralizing antibody (NP-HEV[ aIL21] ) to draining LN and kidney allografts resulting in improved graft function and recipient survival. The NP-HEV[aIL21] system also decreased alloreactive B cell responses, donor-specific antibody production, and ABMR-like lesions in kidney grafts. CONCLUSION Our study provides a therapeutic strategy to selectively target distinct effector sites to attenuate B-cell alloimmunity while limiting effects of broad systemic immunosuppression in kidney transplantation.

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来源期刊

Kidney international 医学-泌尿学与肾脏学

CiteScore

23.30

自引率

3.10%

发文量

490

审稿时长

3-6 weeks

期刊介绍： Kidney International (KI), the official journal of the International Society of Nephrology, is led by Dr. Pierre Ronco (Paris, France) and stands as one of nephrology's most cited and esteemed publications worldwide. KI provides exceptional benefits for both readers and authors, featuring highly cited original articles, focused reviews, cutting-edge imaging techniques, and lively discussions on controversial topics. The journal is dedicated to kidney research, serving researchers, clinical investigators, and practicing nephrologists.