RT Journal Article
SR Electronic
T1 TIGIT-Fc Promote Immune Tolerance at the Feto-maternal Interface
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 819243
DO 10.1101/819243
A1 Fu, Wenyan
A1 Ma, Zetong
A1 Lei, Changhai
A1 Ding, Min
A1 Hu, Shi
YR 2019
UL http://biorxiv.org/content/early/2019/10/28/819243.abstract
AB The perfect synchronization of maternal immune-endocrine mechanisms and those of the foetus is necessary for a successful pregnancy. In this report, decidual immune cells at the maternal-foetal interface were detected that expressed TIGIT (T cell immunoreceptor with Ig and ITIM domains), which is a co-inhibitory receptor that triggers immunological tolerance. We generated recombinant TIGIT-Fc fusion proteins by linking the extracellular domain of TIGIT and silent Fc fragments. The treatment with TIGIT-Fc of human decidual dendritic cells (dDCs) increased the production of interleukin 10 and induced the dDCs to powerfully polarize the decidual CD4+ T cells towards a classic TH2 phenotype. The administration of TIGIT-Fc to CBA/J pregnant mice at preimplantation induced CD4+ forkhead box P3+ (Foxp3+) regulatory T cells and tolerogenic dendritic cells and increased pregnancy rates in a mouse model of abortive stress. Moreover, we proposed that progesterone play a direct role in the transcriptional regulation of the TIGIT gene in decidual immune cell subsets. The results suggested the therapeutic potential of the TIGIT-Fc fusion protein in reinstating immune tolerance in failing pregnancies.