Interleukin-33-induced expression of PIBF1 by decidual B cells protects against preterm labor

Bihui Huang, Wayne State University
Azure N. Faucette, Wayne State University
Michael D. Pawlitz, Wayne State University
Bo Pei, Wayne State University
Joshua W. Goyert, Wayne State University
Jordan Zheng Zhou, Wayne State University
Nadim G. El-Hage, Wayne State University
Jie Deng, Yale School of Medicine
Jason Lin, Wayne State University
Fayi Yao, Wayne State University
Robert S. Dewar, Wayne State University
Japnam S. Jassal, Wayne State University
Maxwell L. Sandberg, Union College, Schenectady
Jing Dai, Wayne State University
Montserrat Cols, Memorial Sloan-Kettering Cancer Center
Cong Shen, Memorial Sloan-Kettering Cancer Center
Lisa A. Polin, Wayne State University
Ronald A. Nichols, Wayne State University
Theodore B. Jones, Wayne State University
Martin H. Bluth, Wayne State University
Karoline S. Puder, Wayne State University
Bernard Gonik, Wayne State University
Nihar R. Nayak, Wayne State University
Elizabeth Puscheck, Wayne State University
Wei Zen Wei, Wayne State University
Andrea Cerutti, Parc de Recerca Biomèdica de Barcelona
Marco Colonna, National Institute of Allergy and Infectious Diseases (NIAID)
Kang Chen, Wayne State University

Abstract

© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. 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.