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Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses – proteomics data

ABSTRACT: In this study, the participation of fetal factors in maintaining the immune balance during gestation was investigated by assessing the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

SUBMITTER: Isabel Karkossa

LAB HEAD: Kristin Schubert

PROVIDER: PXD035883 | Pride | 2022-10-14

REPOSITORIES: Pride

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Human chorionic gonadotropin promotes murine Treg cells and restricts pregnancy-harmful proinflammatory Th17 responses.

Lentz Lea S LS Stutz Annika J AJ Meyer Nicole N Schubert Kristin K Karkossa Isabel I von Bergen Martin M Zenclussen Ana C AC Schumacher Anne A

Frontiers in immunology 20220920

An equilibrium between proinflammatory and anti-inflammatory immune responses is essential for maternal tolerance of the fetus throughout gestation. To study the participation of fetal tissue-derived factors in this delicate immune balance, we analyzed the effects of human chorionic gonadotropin (hCG) on murine Treg cells and Th17 cells <i>in vitro</i>, and on pregnancy outcomes, fetal and placental growth, blood flow velocities and remodeling of the uterine vascular bed <i>in vivo</i>. Compared ...[more]

PMID: 36203576

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Project description:To explore chorionic gonadotropin (CG)-regulated gene expression in the primate corpus luteum (CL), adult female rhesus macaques were treated with a model of simulated early pregnancy (SEP). Total RNA was isolated from individual CL and hybridized to AffymetrixM-bM-^DM-" GeneChip Rhesus Macaque Genome Arrays The level of 1192 transcripts changed expression > 2-fold (one-way ANOVA, FDR correction; P<0.05) during SEP when compared to Day 10 untreated controls, and the majority of changes occurred between Days 10 and 12 of SEP. To compare transcript levels between SEP rescued and regressing CL, previously banked rhesus GeneChip array data from the mid- to late and very late luteal phase were analyzed with time-matched intervals in SEP. Comparing RMA-normalized transcripts from the natural cycle with those from luteal rescue revealed 7677 transcripts changing in expression pattern >2 fold (one-way ANOVA, FDR correction; P<0.05) between the two groups. Clustering of samples revealed that the SEP samples possessed the most related transcript expression profiles. Regressed CL (days 18-19, around menses) were the most unlike all other CL. The most affected KEGG pathway was Steroid Biosynthesis, and most significantly absent pathways following SEP treatment includes groups of genes whose products promote cell-death. By further comparing the genome-wide changes in luteal gene expression during rescue in SEP, with those in CL during luteolysis in the natural menstrual cycle, it is possible to identify key regulatory pathways promoting fertility. Simulated early pregnancy (SEP) treatment was begun on day 9 as Duffy and Stouffer (1997) by treatment of females with recombinant human chorionic gonadotropin (hCG; NovarelM-bM-^DM-", Ferring Pharmaceuticals Inc. Parsippany, NJ, USA) in increasing dosages (15, 30,45,90,180,360,720,1440, and 2880 IU) twice daily by intramuscular injection. CL were collected by laparotomy on days 10, 12, 15, and 18, representing 1, 3, 6 and 9 days of hCG treatment (n=4 CL/day). Additionally, luteal day 10 untreated CL were collected to serve as baseline controls for SEP CL. All CL were dissected away from luteal tissue, sectioned, and snap-frozen in liquid nitrogen and stored at -80M-BM-0C until RNA and protein isolation by TRIzolM-BM-. extraction (Invitrogen, Carlsbad, CA, USA) according to manufacturerM-bM-^@M-^Ys protocols.

			Action	DRS
	20210218_Uniprot_MusMusculus_REFSET_IK.fasta	Fasta
	Set1_MD10_f1.raw	Raw
	Set1_MD10_f2.raw	Raw
	Set1_MD11_f1.raw	Raw
	Set1_MD11_f2.raw	Raw