The role of donor-derived exosomes in lung allograft rejection

Ranjithkumar Ravichandran, Sandhya Bansal, Mohammad Rahman, Monal Sharma, Wei Liu, Ankit Bharat, Ramsey Hachem, Ashraf Omar, Michael A. Smith, T. Mohanakumar

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30% of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors—resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD.

Original languageEnglish (US)
JournalHuman Immunology
DOIs
StatePublished - Jan 1 2019

Fingerprint

Exosomes
Allografts
Tissue Donors
Lung
Autoantigens
Antibodies
HLA Antigens
Antigens
Transplants
Antigen Presentation
Proteasome Endopeptidase Complex
Tubulin
MicroRNAs
Autoimmunity

Keywords

  • Autoimmune
  • CLAD
  • Exosomes
  • Self-antigens
  • Transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Ravichandran, R., Bansal, S., Rahman, M., Sharma, M., Liu, W., Bharat, A., ... Mohanakumar, T. (2019). The role of donor-derived exosomes in lung allograft rejection. Human Immunology. https://doi.org/10.1016/j.humimm.2019.03.012
Ravichandran, Ranjithkumar ; Bansal, Sandhya ; Rahman, Mohammad ; Sharma, Monal ; Liu, Wei ; Bharat, Ankit ; Hachem, Ramsey ; Omar, Ashraf ; Smith, Michael A. ; Mohanakumar, T. / The role of donor-derived exosomes in lung allograft rejection. In: Human Immunology. 2019.
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abstract = "Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30{\%} of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors—resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD.",
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Ravichandran, R, Bansal, S, Rahman, M, Sharma, M, Liu, W, Bharat, A, Hachem, R, Omar, A, Smith, MA & Mohanakumar, T 2019, 'The role of donor-derived exosomes in lung allograft rejection', Human Immunology. https://doi.org/10.1016/j.humimm.2019.03.012

The role of donor-derived exosomes in lung allograft rejection. / Ravichandran, Ranjithkumar; Bansal, Sandhya; Rahman, Mohammad; Sharma, Monal; Liu, Wei; Bharat, Ankit; Hachem, Ramsey; Omar, Ashraf; Smith, Michael A.; Mohanakumar, T.

In: Human Immunology, 01.01.2019.

Research output: Contribution to journalReview article

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T1 - The role of donor-derived exosomes in lung allograft rejection

AU - Ravichandran, Ranjithkumar

AU - Bansal, Sandhya

AU - Rahman, Mohammad

AU - Sharma, Monal

AU - Liu, Wei

AU - Bharat, Ankit

AU - Hachem, Ramsey

AU - Omar, Ashraf

AU - Smith, Michael A.

AU - Mohanakumar, T.

PY - 2019/1/1

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N2 - Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30% of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors—resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD.

AB - Lung transplant recipients (LTxRs) with acute or chronic rejection release circulating exosomes that mostly originate from donor lung tissue and express mismatched human leucocyte antigens (HLA) and lung-associated self-antigens (SAgs), Collagen-V and K alpha 1 Tubulin. During lung transplant (LTx), donor lungs often undergo injuries that increase the antigenicity of the transplanted organ. 30% of LTxRs also have pre-transplant antibodies (Abs) to HLA and lung SAgs, which may induce conditions that increase the risk of chronic lung allograft dysfunction (CLAD). Post-transplant, some recipients experience de novo development of Abs to mismatched donor HLA (donor-specific antibody [DSA]) and Abs to lung SAgs, which have been implicated in CLAD pathogenesis. Because most LTxRs who develop DSA also develop Abs to SAgs, some have suggested a synergistic relationship between alloimmunity and autoimmunity in CLAD immunopathogenesis. These processes likely occur from stress-induced exosome release. Exosomes carry allo-antigens, lung SAgs, several micro RNAs, proteasome, co-stimulatory molecules, and pro-inflammatory transcription factors—resulting in efficient antigen presentation by direct, semidirect, and indirect pathways, leading to immune responses to both allo-antigens and lung-associated SAgs. This review summarizes recent findings on the role of exosomes, and processes triggering immune responses to allo-antigens and lung SAgs that ultimately culminate in CLAD.

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KW - Exosomes

KW - Self-antigens

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