# Complement-Mediated Exosome Function in Transplantation

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2022 · $565,013

## Abstract

Project Summary
T cell mediated graft rejection remains a critical barrier to long-term graft health and survival. Post-transplant
complement-induced priming of T cells and the transfer of donor major histocompatibility complexes (MHC) to
recipient dendritic cells (DCs) by graft-released exosomes (commonly referred to as “cross dressing”) are both
mechanistically involved in the generation of anti-donor cellular immunity. Our preliminary data newly implicate
mannose binding lectin (MBL) pathway-dependent complement activation as necessary mediator for
complement opsonization of exosomes and exosome-mediated donor MHC delivery to recipient DCs.
Together with our prior observation that recipient MBL pathway complement activation is required for
generation of robust anti-donor T cell responses and costimulatory-blockade resistant graft rejection, these
data lead to our central hypothesis that post transplant MBL pathway-initiated complement activation deposits
complement opsonins on exosomes, which bind to recipient DCs via complement receptors, and that this
process optimizes DC “cross dressing” to permit semi-direct pathway anti-donor T cell immunity and ultimately
allograft rejection. We will test this hypothesis in two specific aims. In aim 1 we will study the mechanisms
required for complement activation on exosomes, characterize the effect of complement opsonins on exosome
binding to recipient DCs, and test the role of DC-expressed complement receptors in our model. In aim 2 we
will test for links between complement-mediated DC “cross dressing” and post-transplant anti-donor T cell
immunity and transplant outcomes. The findings will be significant because a) they will provide fundamental
insights into the biology of exosome function, b) provide mechanistic links between exosomes, complement,
and adaptive T cell immunity, and c) potentially identify novel treatment strategies and therapeutic targets to
improve transplant outcomes. Our proposal is conceptually innovative and tests a novel paradigm linking
exosome function and complement activation that may have broad implications beyond the field of
transplantation.

## Key facts

- **NIH application ID:** 10563092
- **Project number:** 1R01AI172899-01
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Nicholas Chun
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $565,013
- **Award type:** 1
- **Project period:** 2022-09-22 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10563092

## Citation

> US National Institutes of Health, RePORTER application 10563092, Complement-Mediated Exosome Function in Transplantation (1R01AI172899-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10563092. Licensed CC0.

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