title: Interleukin-33-induced expression of PIBF1 by decidual B cells protects against preterm labor.
abstract: Preterm birth (PTB) is a leading cause of neonatal death worldwide. Intrauterine and systemic infection and inflammation cause 30-40% of spontaneous preterm labor (PTL), which precedes PTB. Although antibody production is a major immune defense mechanism against infection, and B cell dysfunction has been implicated in pregnancy complications associated with PTL, the functions of B cells in pregnancy are not well known. We found that choriodecidua of women undergoing spontaneous PTL harbored functionally altered B cell populations. B cell-deficient mice were markedly more susceptible than wild-type (WT) mice to PTL after inflammation, but B cells conferred interleukin (IL)-10-independent protection against PTL. B cell deficiency in mice resulted in a lower uterine level of active progesterone-induced blocking factor 1 (PIBF1), and therapeutic administration of PIBF1 mitigated PTL and uterine inflammation in B cell-deficient mice. B cells are a significant producer of PIBF1 in human choriodecidua and mouse uterus in late gestation. PIBF1 expression by B cells is induced by the mucosal alarmin IL-33 (ref. 9). Human PTL was associated with diminished expression of the α-chain of IL-33 receptor on choriodecidual B cells and a lower level of active PIBF1 in late gestation choriodecidua. These results define a vital regulatory cascade involving IL-33, decidual B cells and PIBF1 in safeguarding term pregnancy and suggest new therapeutic approaches based on IL-33 and PIBF1 to prevent human PTL.
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Bihui
authors.initials: B
authors.lastname: Huang
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Azure N
authors.initials: AN
authors.lastname: Faucette
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Pawlitz
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Pei
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Goyert
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Jordan Zheng
authors.initials: JZ
authors.lastname: Zhou
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Nadim G
authors.initials: NG
authors.lastname: El-Hage
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, New Haven, Connecticut, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Fayi
authors.initials: F
authors.lastname: Yao
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Dewar
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Japnam S
authors.initials: JS
authors.lastname: Jassal
authors.affiliation: Leadership in Medicine Program, Union College, Schenectady, New York, USA.
authors.forename: Maxwell L
authors.initials: ML
authors.lastname: Sandberg
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Dai
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Montserrat
authors.initials: M
authors.lastname: Cols
authors.affiliation: Immunology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
authors.forename: Cong
authors.initials: C
authors.lastname: Shen
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Polin
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.|Department of Obstetrics and Gynecology-Med Ed, Beaumont Dearborn Hospital, Dearborn, Michigan, USA.
authors.forename: Ronald A
authors.initials: RA
authors.lastname: Nichols
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.|Department of Obstetrics and Gynecology-Med Ed, Beaumont Dearborn Hospital, Dearborn, Michigan, USA.
authors.forename: Theodore B
authors.initials: TB
authors.lastname: Jones
authors.affiliation: Department of Pathology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Martin H
authors.initials: MH
authors.lastname: Bluth
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Karoline S
authors.initials: KS
authors.lastname: Puder
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Bernard
authors.initials: B
authors.lastname: Gonik
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Nihar R
authors.initials: NR
authors.lastname: Nayak
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Puscheck
authors.affiliation: Department of Oncology, Wayne State University, Detroit, Michigan, USA.
authors.forename: Wei-Zen
authors.initials: WZ
authors.lastname: Wei
authors.affiliation: Catalan Institute for Research and Advanced Studies, Barcelona Biomedical Research Park, Barcelona, Spain.|Program for Inflammatory and Cardiovascular Disorders, Institut Hospital del Mar d'Investigacions Mèdiques, Barcelona, Spain.|Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.|Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cerutti
authors.affiliation: Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.|Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.affiliation: Department of Obstetrics and Gynecology, Wayne State University, Detroit, Michigan, USA.|Department of Oncology, Wayne State University, Detroit, Michigan, USA.|Mucosal Immunology Studies Team, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Kang
authors.identifier: 0000-0001-9892-3118
authors.initials: K
authors.lastname: Chen
mesh_terms: D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D003656:Decidua / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000276:immunology / Q000378:metabolism; D000067596:Interleukin-33 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D007752:Obstetric Labor, Premature / Q000276:immunology / Q000378:metabolism*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000276:immunology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; C491677:Pibf1 protein, mouse; D011257:Pregnancy Proteins