title: Amnion cell-mediated immune modulation following bleomycin challenge: controlling the regulatory T cell response.
abstract: BACKGROUND
  The immunomodulatory properties of human amnion epithelial cells (hAECs) have been previously described in several disease models. We previously reported on the ability of hAECs to influence macrophage phenotype and chemotaxis. In this study, we aim to elucidate the contribution of regulatory T cells (Tregs) to macrophage polarisation and downstream effects on inflammation and fibrosis in a bleomycin model of lung injury.
  
  
  METHODS
  Either CD45(+)/FoxP3(+) Tregs or CD45(+)/FoxP3 (-) non-Tregs were adoptively transferred into Rag1 (-/-) mice immediately prior to bleomycin challenge. Four million hAECs were administered 24 hours later. Outcomes were measured 7 or 14 days later.
  
  
  RESULTS
  Mitigation of lung inflammation and fibrosis was observed only in animals that received both hAECs and Tregs. hAEC treatment also induced the maturation of non-Tregs into FoxP3-expressing Tregs. This event was found to be transforming growth factor-beta (TGFβ)-dependent. Furthermore, polarisation of macrophages from M1 to M2 occurred only in animals that received hAECs and Tregs.
  
  
  CONCLUSIONS
  This study provides the first evidence that Tregs are required for hAEC-mediated macrophage polarisation and consequential mitigation of bleomycin-induced lung injury. Uncovering the interactions between hAECs, macrophages, and T-cell subsets is central to understanding the mechanisms by which hAECs elicit lung repair.
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. jean.tan@monash.edu.
authors: Jean L
authors: JL
authors: Tan
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. siow.chan@monash.edu.
authors: Siow T
authors: ST
authors: Chan
authors: Monash Micro Imaging, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. camden.low@monash.edu.
authors: Camden Y
authors: CY
authors: Lo
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. james.deane@monash.edu.|Department of Obstetrics and Gynecology, Monash University, 246 Clayton Rd, Clayton, Victoria, 3168, Australia. james.deane@monash.edu.
authors: James A
authors: JA
authors: Deane
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. courtney.mcdonald@monash.edu.|Department of Obstetrics and Gynecology, Monash University, 246 Clayton Rd, Clayton, Victoria, 3168, Australia. courtney.mcdonald@monash.edu.
authors: Courtney A
authors: CA
authors: McDonald
authors: Australian Regenerative Medicine Institute, Building 75, Wellington Rd, Clayton, Victoria, 3168, Australia. claude.bernard@monash.edu.
authors: Claude Ca
authors: CC
authors: Bernard
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. euan.wallace@monash.edu.|Department of Obstetrics and Gynecology, Monash University, 246 Clayton Rd, Clayton, Victoria, 3168, Australia. euan.wallace@monash.edu.
authors: Euan M
authors: EM
authors: Wallace
authors: The Ritchie Centre, Monash Institute of Medical Research, Monash University, 27-31 Wright St, Clayton, Victoria, 3168, Australia. rebecca.lim@monash.edu.|Department of Obstetrics and Gynecology, Monash University, 246 Clayton Rd, Clayton, Victoria, 3168, Australia. rebecca.lim@monash.edu.
authors: Rebecca
authors: R
authors: Lim
mesh_terms: D000650:Amnion / Q000166:cytology*; D000818:Animals; D001761:Bleomycin / Q000633:toxicity*; D002454:Cell Differentiation; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005355:Fibrosis; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007249:Inflammation; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008168:Lung / Q000166:cytology; D055370:Lung Injury / Q000209:etiology*; D008264:Macrophages / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D018398:Homeodomain Proteins; D016212:Transforming Growth Factor beta; D001761:Bleomycin; C064658:RAG-1 protein; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human
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