Presence of Donor Lymph Nodes Within Vascularized Composite Allotransplantation Ameliorates VEGF-C-mediated Lymphangiogenesis and Delays the Onset of Acute Rejection.

Olariu, Radu; Tsai, Catherine; Abd El Hafez, Mai Moustafa Ahmed; Milusev, Anastasia; Banz, Yara; Lese, Ioana; Leckenby, Jonathan Ian; Constantinescu, Mihai; Rieben, Robert; Vögelin, Esther; Taddeo, Adriano (2021). Presence of Donor Lymph Nodes Within Vascularized Composite Allotransplantation Ameliorates VEGF-C-mediated Lymphangiogenesis and Delays the Onset of Acute Rejection. Transplantation, 105(8), pp. 1747-1759. Lippincott Williams & Wilkins 10.1097/TP.0000000000003601

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BACKGROUND

The lymphatic system plays an active role in modulating inflammation in autoimmune diseases and organ rejection. In this work, we hypothesized that the transfer of donor lymph node (LN) might be used to promote lymphangiogenesis and influence rejection in vascularized composite allotransplantation (VCA).

METHODS

Hindlimb transplantations were performed in which (1) recipient rats received VCA containing donor LN (D:LN+), (2) recipient rats received VCA depleted of all donor LN (D:LN-), and (3) D:LN+ transplantations were followed by lymphangiogenesis inhibition using a vascular endothelial growth factor receptor-3 (VEGFR3) blocker.

RESULTS

Our data show that graft rejection started significantly later in D:LN+ transplanted rats as compared to the D:LN- group. Moreover, we observed a higher level of VEGF-C and a quicker and more efficient lymphangiogenesis in the D:LN+ group as compared to the D:LN- group. The presence of donor LN within the graft was associated with reduced immunoactivation in the draining LN and increased frequency of circulating and skin-resident donor T regulatory cells. Blocking of the VEGF-C pathway using a VEGFR3 blocker disrupts the lymphangiogenesis process, accelerates rejection onset, and interferes with donor T-cell migration.

CONCLUSIONS

This study demonstrates that VCA LNs play a pivotal role in the regulation of graft rejection and underlines the potential of specifically targeting the LN component of a VCA to control graft rejection.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Handchirurgie
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Hand Surgery
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery > Plastic, Reconstructive and Aesthetic Surgery
04 Faculty of Medicine > Service Sector > Institute of Pathology
04 Faculty of Medicine > Department of Orthopaedic, Plastic and Hand Surgery (DOPH) > Clinic of Plastic and Hand Surgery
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Plastische Chirurgie
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50

UniBE Contributor:

Olariu, Radu; Tsai, Catherine; Abd El Hafez, Mai Moustafa Ahmed; Milusev, Anastasia; Banz Wälti, Yara; Lese, Ioana; Leckenby, Jonathan Ian; Constantinescu, Mihai Adrian; Rieben, Robert; Vögelin, Esther and Taddeo, Adriano

Subjects:

600 Technology > 630 Agriculture
600 Technology > 610 Medicine & health

ISSN:

0041-1337

Publisher:

Lippincott Williams & Wilkins

Language:

English

Submitter:

Veronika Picha

Date Deposited:

28 Jul 2021 13:43

Last Modified:

28 Jul 2021 14:22

Publisher DOI:

10.1097/TP.0000000000003601

PubMed ID:

34291766

BORIS DOI:

10.48350/157724

URI:

https://boris.unibe.ch/id/eprint/157724

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