bims-reprim 2020-10-25 papers

Issue of 2020–10–25
three papers selected by
Iva Filipovic, Karolinska Institutet

J Exp Med. 2021 Jan 04. pii: e20200891. [Epub ahead of print]218(1):

Phenotypic and functional characterization of first-trimester human placental macrophages, Hofbauer cells.

Jake R Thomas, Anna Appios, Xiaohui Zhao, Roksana Dutkiewicz, Maria Donde, Colin Y C Lee, Praveena Naidu, Christopher Lee, Joana Cerveira, Bing Liu, Florent Ginhoux, Graham Burton, Russell S Hamilton, Ashley Moffett, Andrew Sharkey, Naomi McGovern.

Hofbauer cells (HBCs) are a population of macrophages found in high abundance within the stroma of the first-trimester human placenta. HBCs are the only fetal immune cell population within the stroma of healthy placenta. However, the functional properties of these cells are poorly described. Aligning with their predicted origin via primitive hematopoiesis, we find that HBCs are transcriptionally similar to yolk sac macrophages. Phenotypically, HBCs can be identified as HLA-DR-FOLR2+ macrophages. We identify a number of factors that HBCs secrete (including OPN and MMP-9) that could affect placental angiogenesis and remodeling. We determine that HBCs have the capacity to play a defensive role, where they are responsive to Toll-like receptor stimulation and are microbicidal. Finally, we also identify a population of placenta-associated maternal macrophages (PAMM1a) that adhere to the placental surface and express factors, such as fibronectin, that may aid in repair.

DOI: https://doi.org/10.1084/jem.20200891

Am J Reprod Immunol. 2020 Oct 18. e13362

Alteration of Systemic and Uterine Endometrial Immune Populations in Patients with Endometriosis.

Nhung X H Le, Julio R Loret de Mola, Pamela Bremer, Kathleen Groesch, Teresa Wilson, Paula Diaz-Sylvester, Andrea G Braundmeier-Fleming.

PROBLEM: Endometriosis is defined as growth of endometrial tissue in ectopic locations, it is associated with infertility, chronic pain and affects ~12% of reproductive aged women. Although inflammation is known to play a key role in endometriosis, knowledge related to immune phenotypes associated with this disease is lacking. This study aimed to characterize immune profiles in patients with endometriosis, to assess inflammatory mediators and determine if surgical and/or hormonal therapies restore immune homeostasis.
METHODS OF STUDY: Samples from 9 controls and 20 histologically confirmed endometriosis patients were collected upon surgery and ~1-3 weeks post-surgical intervention. Subjects were either not utilizing hormonal suppression or were currently on monophasic hormonal therapy. Tolerant regulatory T-cells (Tregs = natural [nTregs] + inducible [iTregs]) and inflammatory T-helper 17 (Th17) cells were identified in peripheral blood via flow cytometry and within the eutopic/ectopic endometrial tissues via immunohistochemistry and real-time-qPCR. Cytokines were assessed via 10-plex-ELISA.
RESULTS: Patients with endometriosis not utilizing hormonal therapy exhibited lower iTregs (tolerant), greater Th17 (inflammatory) and a reduction in Treg/Th17 ratio (p<0.05), indicative of systemic inflammation. Treg and Th17 localizations were enhanced within the ectopic endometrial implant, which promotes lesion development. Hormonal therapy decreased systemic and local inflammation (eutopic/ectopic endometrium) via decreased iTregs and Th17 cells in patients with endometriosis (p<0.05). Thus, imbalance within immune populations correlated with increased inflammation in patients with endometriosis, which was mitigated by hormonal therapy.
CONCLUSIONS: Patients with endometriosis exhibited systemic and localized inflammation within ectopic and endometrial tissues. Hormonal therapy dampened inflammation caused by disease.

Keywords: Endometriosis; T helper 17; hormonal therapy; regulatory T cell; surgical intervention

DOI: https://doi.org/10.1111/aji.13362

Sci Rep. 2020 Oct 20. 10(1): 17819

Longitudinal plasma inflammatory proteome profiling during pregnancy in the Born into Life study.

Anna M Hedman, Cecilia Lundholm, Ellika Andolf, Göran Pershagen, Tove Fall, Catarina Almqvist.

The maternal immune system is going through considerable changes during pregnancy. However, little is known about the determinants of the inflammatory proteome and its relation to pregnancy stages. Our aim was to investigate the plasma inflammatory proteome before, during and after pregnancy. In addition we wanted to test whether maternal and child outcomes were associated with the proteome. A cohort of 94 healthy women, enrolled in a longitudinal study with assessments at up to five time points around pregnancy, ninety-two inflammatory proteins were analysed in plasma with a multiplex Proximity Extension Assay. First, principal components analysis were applied and thereafter regression modelling while correcting for multiple testing. We found profound shifts in the overall inflammatory proteome associated with pregnancy stage after multiple testing (p < .001). Moreover, maternal body mass index (BMI) was associated with inflammatory proteome primarily driven by VEGFA, CCL3 and CSF-1 (p < .05). The levels of most inflammatory proteins changed substantially during pregnancy and some of these were related to biological processes such as regulation of immune response. Maternal BMI was significantly associated with higher levels of three inflammation proteins calling for more research in the interplay between pregnancy, inflammation and BMI.

DOI: https://doi.org/10.1038/s41598-020-74722-5