title: The majority of murine γδ T cells at the maternal-fetal interface in pregnancy produce IL-17.
abstract: Compared with lymphoid tissues, the immune cell compartment at mucosal sites is enriched with T cells bearing the γδ T-cell receptor (TCR). The female reproductive tract, along with the placenta and uterine decidua during pregnancy, are populated by γδ T cells predominantly expressing the invariant Vγ6(+)Vδ1(+) receptor. Surprisingly little is understood about the function of these cells. We found that the majority of γδ T cells in the non-pregnant uterus, pregnant uterus, decidua and placenta of mice express the transcription factor RORγt and produce interleukin-17 (IL-17). In contrast, IFNγ-producing γδ T cells were markedly reduced in gestational tissues compared with uterine-draining lymph nodes and spleen. Both uterine-resident invariant Vγ6(+) and Vγ4(+) γδ T cells which are more typically found in lymphoid tissues and circulating blood, were found to express IL-17. Vγ4(+) γδ T cells were particularly enriched in the placenta, suggesting a pregnancy-specific recruitment or expansion of these cells. A small increase in IL-17-producing γδ T cells was observed in allogeneic compared with syngeneic pregnancy, suggesting a contribution to regulating the maternal response to paternally-derived alloantigens. However, their high proportions also in non-pregnant uteri and gestational tissues of syngeneic pregnancy imply a role in the prevention of intrauterine infection or quality control of fetal development. These data suggest the need for a more rigorous evaluation of the role of IL-17 in sustaining normal pregnancy, particularly as emerging data points to a pathogenic role for IL-17 in pre-eclampsia, pre-term birth, miscarriage and maternal immune activation-induced behavioral abnormalities in offspring.
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Gabriela V
authors.initials: GV
authors.lastname: Pinget
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Corpuz
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
authors.forename: Jessica
authors.initials: J
authors.lastname: Stolp
authors.affiliation: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Experimental Therapeutics Laboratory, Hanson Institute, Royal Adelaide Hospital, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Lousberg
authors.affiliation: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA, Australia.|Experimental Therapeutics Laboratory, Hanson Institute, Royal Adelaide Hospital, and Sansom Institute, School of Pharmacy and Medical Science, University of South Australia, Adelaide, SA, Australia.
authors.forename: Kerrilyn R
authors.initials: KR
authors.lastname: Diener
authors.affiliation: The Robinson Research Institute and School of Medicine, University of Adelaide, Adelaide, SA, Australia.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Robertson
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sprent
authors.affiliation: Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.|St Vincent's Clinical School, University of New South Wales, Sydney, NSW, Australia.
authors.forename: Kylie E
authors.initials: KE
authors.lastname: Webster
mesh_terms: D000818:Animals; D005260:Female; D020381:Interleukin-17 / Q000096:biosynthesis*; D008431:Maternal-Fetal Exchange / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
chemical_list: D020381:Interleukin-17; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D016692:Receptors, Antigen, T-Cell, gamma-delta