title: Imbalance of placental regulatory T cell and Th17 cell population dynamics in the FIV-infected pregnant cat.
abstract: BACKGROUND
  An appropriate balance in placental regulatory T cells (Tregs), an immunosuppressive cell population, and Th17 cells, a pro-inflammatory cell population, is essential in allowing tolerance of the semi-allogeneic fetus. TGF-β and IL-6 are cytokines that promote differentiation of Tregs and Th17 cells from a common progenitor; aberrant expression of the cytokines may perturb the balance in the two cell populations. We previously reported a pro-inflammatory placental environment with decreased levels of FoxP3, a Treg marker, and increased levels of IL-6 in the placentas of FIV-infected cats at early pregnancy. Thus, we hypothesized that FIV infection in the pregnant cat causes altered placental Treg and Th17 cell populations, possibly resulting in placental inflammation.
  
  
  METHODS
  We examined the effect of FIV infection on Treg and Th17 populations in placentas at early pregnancy using quantitative confocal microscopy to measure FoxP3 or RORγ, a Th17 marker, and qPCR to quantify expression of the key cytokines TGF-β and IL-6.
  
  
  RESULTS
  FoxP3 and RORγ were positively correlated in FIV-infected placentas at early pregnancy, but not placentas from normal cats, indicating virus-induced alteration in the balance of these cell populations. In control cats the expression of IL-6 and RORγ was positively correlated as predicted, but this relationship was disrupted in infected animals. TGF-β was reduced in infected queens, an occurrence that could dysregulate both Treg and Th17 cell populations. Co-expression analyses revealed a highly significant positive correlation between IL-6 and TGF-β expression in control animals that did not occur in infected animals.
  
  
  CONCLUSIONS
  Collectively, these data point toward potential disruption in the balance of Treg and Th17 cell populations that may contribute to FIV-induced inflammation in the feline placenta.
authors.affiliation: Department of Biological Sciences, Mississippi State University, PO Box GY, Mississippi State, MS 39762, USA.
authors.forename: Crystal E
authors.initials: CE
authors.lastname: Boudreaux
authors.forename: Lyndon B
authors.initials: LB
authors.lastname: Chumbley
authors.forename: Veronica L
authors.initials: VL
authors.lastname: Scott
authors.forename: Dwayne A
authors.initials: DA
authors.lastname: Wise
authors.forename: Karen S
authors.initials: KS
authors.lastname: Coats
mesh_terms: D000818:Animals; D002415:Cats; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000473:pathology; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis; D020869:Gene Expression Profiling; D016089:Immunodeficiency Virus, Feline / Q000276:immunology* / Q000472:pathogenicity; D015850:Interleukin-6 / Q000096:biosynthesis; D018613:Microscopy, Confocal; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000032:analysis; D010920:Placenta / Q000276:immunology* / Q000473:pathology; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D015850:Interleukin-6; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016212:Transforming Growth Factor beta