Aging dysregulates neutrophil extracellular trap formation in response to HIV in blood and genital tissues.

Women acquire HIV through sexual transmission, with increasing incidence in women >50 years old. Identifying protective mechanisms in the female genital tract (FGT) is important to prevent HIV-acquisition in women as they age. Human genital and blood neutrophils inactivate HIV by releasing neutrophil extracellular traps (NETs), an innate protective mechanism against HIV-infection.

Decidualized human decidual stromal cells inhibit chemotaxis of activated T cells: a potential mechanism of maternal-fetal immune tolerance.

Background: Numerous lines of evidence confirm that decidual stromal cells (DSCs) play a key role in maternal-fetal immune tolerance. Under the influence of progesterone and other hormones, the DSCs go through a process of differentiation (decidualization) during normal pregnancy. In mice, DSCs inhibit the expression of chemokines that attract abortigenic Th1 and Tc cells to the decidua.

Relevance of , CD163/CD206, and CD33 in clinical severity stratification of COVID-19.

Background: Approximately 13.8% and 6.1% of coronavirus disease 2019 (COVID-19) patients require hospitalization and sometimes intensive care unit (ICU) admission, respectively.

Inhibition of BMP2 and BMP4 Represses Barrett's Esophagus While Enhancing the Regeneration of Squamous Epithelium in Preclinical Models.

Background & Aims: Barrett's esophagus is considered to be a metaplastic lesion that predisposes for esophageal adenocarcinoma. Development of Barrett's esophagus is considered to be driven by sonic hedgehog mediated bone morphogenetic protein (BMP) signaling. We aimed to investigate in preclinical in vivo models whether targeting canonical BMP signaling could be an effective treatment for Barrett's esophagus.

Influence of the ectopic location on the antigen expression and functional characteristics of endometrioma stromal cells.

Research Question: Are the alterations observed in the endometriotic cells, such as progesterone resistance, already present in the eutopic endometrium or acquired in the ectopic location?

Design: The response to decidualization with progesterone and cyclic AMP for up to 28 days was compared in different endometrial stromal cell (EnSC) lines established from samples of endometriomas (eEnSC), eutopic endometrium from women with endometriosis (eBEnSC), endometrial tissue from healthy women (BEnSC) and menstrual blood from healthy donors (mEnSC).

Results: Usual features of decidualized cells, such as changes in cell morphology and expression of prolactin, were similarly observed in the three types of eutopic EnSC studied, but not in the ectopic cells upon decidualization. Among the phenotypic markers analysed, CD105 was down-regulated under decidualization in all cell types (mEnSC, P = 0.

Stromal cells of the endometrium and decidua: in search of a name and an identity†.

Human endometrial and decidual stromal cells are the same cells in different environments (nonpregnancy and pregnancy, respectively). Although some authors consider decidual stromal cells to arise solely from the differentiation of endometrial stromal cells, this is a debatable issue given that decidualization processes do not end with the formation of the decidua, as shown by the presence of stromal cells from both the endometrium and decidua in both undifferentiated (nondecidualized) and decidualized states. Furthermore, recent functional and transcriptomic results have shown that there are differences in the decidualization process of endometrial and decidual stromal cells, with the latter having a greater decidualization capacity than the former.

SLAMF8 Downregulates Mouse Macrophage Microbicidal Mechanisms PI3K Pathways.

Signaling lymphocytic activation molecule family 8 (SLAMF8) is involved in the negative modulation of NADPH oxidase activation. However, the impact of SLAMF8 downregulation on macrophage functionality and the microbicide mechanism remains elusive. To study this in depth, we first analyzed NADPH oxidase activation pathways in wild-type and SLAMF8-deficient macrophages upon different stimulus.

Decidualization modulates the mesenchymal stromal/stem cell and pericyte characteristics of human decidual stromal cells. Effects on antigen expression, chemotactic activity on monocytes and antitumoral activity.

Decidual stromal cells (DSCs) are the most abundant cellular component of human decidua and play a central role in maternal-fetal immune tolerance. Antigen phenotyping and functional studies recently confirmed the relationship of DSCs with mesenchymal stem/stromal cells (MSCs) and pericytes, the latter two cell types being closely related or identical. The present study investigated the effect of decidualization, a process of cell differentiation driven by progesterone (P4) and other pregnancy hormones, on the MSC/pericyte characteristics of DSCs.

Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature.

Progress in the understanding of the biology of perinatal tissues has contributed to the breakthrough revelation of the therapeutic effects of perinatal derivatives (PnD), namely birth-associated tissues, cells, and secreted factors. The significant knowledge acquired in the past two decades, along with the increasing interest in perinatal derivatives, fuels an urgent need for the precise identification of PnD and the establishment of updated consensus criteria policies for their characterization. The aim of this review is not to go into detail on preclinical or clinical trials, but rather we address specific issues that are relevant for the definition/characterization of perinatal cells, starting from an understanding of the development of the human placenta, its structure, and the different cell populations that can be isolated from the different perinatal tissues.

Menstrual blood-derived stromal cells modulate functional properties of mouse and human macrophages.

Menstrual blood-derived stromal cells (MenSCs) are emerging as a strong candidate for cell-based therapies due to their immunomodulatory properties. However, their direct impact on innate immune populations remains elusive. Since macrophages play a key role in the onset and development of inflammation, understanding MenSCs implication in the functional properties of these cells is required to refine their clinical effects during the treatment of inflammatory disorders.

Inhibitor of apoptosis proteins, NAIP, cIAP1 and cIAP2 expression during macrophage differentiation and M1/M2 polarization.

Monocytes and macrophages constitute the first line of defense of the immune system against external pathogens. Macrophages have a highly plastic phenotype depending on environmental conditions; the extremes of this phenotypic spectrum are a pro-inflammatory defensive role (M1 phenotype) and an anti-inflammatory tissue-repair one (M2 phenotype). The Inhibitor of Apoptosis (IAP) proteins have important roles in the regulation of several cellular processes, including innate and adaptive immunity.

Human predecidual stromal cells have distinctive characteristics of pericytes: Cell contractility, chemotactic activity, and expression of pericyte markers and angiogenic factors.

Introduction: Human decidual stromal cells (DSCs) play a key role in maternal-fetal interactions. Precursors of DSCs (preDSCs) localize around vessels in both the endometrium and decidua. Previous studies suggested a relationship between preDSCs and pericytes because these cells share a perivascular location, alpha smooth muscle actin (α-SM actin) expression and the ability to contract under the effects of cytokines.

Intercellular Adhesion Molecule 1 Regulates Left Ventricular Leukocyte Infiltration, Cardiac Remodeling, and Function in Pressure Overload-Induced Heart Failure.

Background: Left ventricular dysfunction and heart failure are strongly associated in humans with increased circulating levels of proinflammatory cytokines, T cells, and soluble intercellular cell adhesion molecule 1 (ICAM1). In mice, infiltration of T cells into the left ventricle contributes to pathological cardiac remodeling, but the mechanisms regulating their recruitment to the heart are unclear. We hypothesized that ICAM1 regulates cardiac inflammation and pathological cardiac remodeling by mediating left ventricular T-cell recruitment and thus contributing to cardiac dysfunction and heart failure.

Cutting edge: Slamf8 is a negative regulator of Nox2 activity in macrophages.

Slamf8 (CD353) is a cell surface receptor that is expressed upon activation of macrophages (MΦs) by IFN-γ or bacteria. In this article, we report that a very high NADPH oxidase (Nox2) enzyme activity was found in Slamf8(-/-) MΦs in response to Escherichia coli or Staphylococcus aureus, as well as to PMA. The elevated Nox2 activity in Slamf8(-/-) MΦs was also demonstrated in E.

The intestinal antiinflammatory agent glycomacropeptide has immunomodulatory actions on rat splenocytes.

Bovine glycomacropeptide (GMP) is an immunologically active milk peptide that is a part of the normal human diet. GMP has therapeutic value in preclinical models of intestinal inflammation, and its mechanism may be related to effects on lymphocytes. This study focuses on the actions of GMP on rat splenocytes in vitro and in vivo.

Effect of flavonoids on rat splenocytes, a structure-activity relationship study.

Flavonoids are polyphenols frequently consumed in the diet which have been suggested to exert a number of beneficial actions on human health, including intestinal anti-inflammatory activity. Their properties have been studied in numerous cell types, but little is known about their effect on leukocyte biology. We have selected 9 flavonoids (extended to 14 flavonoids plus the related polyphenol resveratrol in some cases) with different structural features to characterize their effects on leukocyte viability, proliferation, and expression of cyclooxygenase 2 (EC 1.

Human decidual stromal cells express HLA-G: Effects of cytokines and decidualization.

Background: Decidual stromal cells (DSC) are the main cellular component of the decidua, the maternal tissue in close contact with fetal trophoblast. Although of mesenchymal origin, DSC exert numerous immune functions that seem to be relevant for the immunological relationship between the mother and fetus. HLA-G, an antigen preferentially expressed by trophoblast, appears to participate in the immune tolerance by the mother of the semiallogeneic fetus.

Follicular dendritic cells are related to bone marrow stromal cell progenitors and to myofibroblasts.

Follicular dendritic cells (FDC) are involved in the presentation of native Ags to B cells during the secondary immune response. Some authors consider FDC to be hemopoietic cells, whereas others believe them to be mesenchymal cells. The low proportion of FDC in the lymphoid follicle, together with technical difficulties in their isolation, make these cells difficult to study.

CD48 controls T-cell and antigen-presenting cell functions in experimental colitis.

Background & Aims: The cell-surface receptor CD48 is a lipid-anchored protein expressed on all antigen-presenting cells and T cells. CD2 and 2B4 are known ligands for CD48, which themselves are expressed on the surface of hematopoietic cells. Here we examine the effect of CD48 in the development of chronic experimental colitis and how CD48 affects adaptive and innate immune functions.

Contractile activity of human decidual stromal cells. II. Effect of interleukin-10.

Context: Human decidual stromal cells (DSC) are myofibroblast-like cells that express alpha-smooth muscle (alpha-SM) actin, a protein associated with cell contractility. Several lines of experimental evidence in humans and mice show that antiinflammatory cytokines favor normal pregnancy, whereas Th1 and inflammatory cytokines play a role in abortion. We previously demonstrated that IL-2, a Th1 cytokine, increased the contractility of human DSC.

In vivo generation of oligoclonal colitic CD4+ T-cell lines expressing a distinct T-cell receptor Vbeta.

Background & Aims: Transplantation of wild-type (H-2k) bone marrow into tg epsilon26 mice (BM-->tg epsilon26) induces colitis, characterized by T-helper cell type 1 activation in the lamina propria. Here we determined whether pathogenic T-cell clones could be derived by serial adoptive transfers into healthy tg epsilon26 recipients, starting with the population of CD4+ cells in the mesenteric lymph nodes of BM-->tg epsilon26 mice.

Methods: CD4+ cells purified from the mesenteric lymph nodes of colitic BM-->tg epsilon26 mice were adoptively transferred into a second group of healthy tg epsilon26 recipients.

Defective B cell responses in the absence of SH2D1A.

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens.

Colitis is associated with thymic destruction attenuating CD4+25+ regulatory T cells in the periphery.

Background & Aims: Syngeneic bone marrow transplantation into the adult tgepsilon26 mouse results in severe wasting disease and colitis. On transplantation, the rudimentary thymus of the adult tgepsilon26 mouse repopulates briefly but quickly regresses in temporal association with the onset of colitis. The aim of this study is to test the hypothesis that treatment of colitis restores thymic capability to generate regulatory T cells (CD4+25+ T(R) cells).

Cutting edge: the natural ligand for glucocorticoid-induced TNF receptor-related protein abrogates regulatory T cell suppression.

CD4(+)25(+) regulatory T (Treg) cells maintain immunological self-tolerance through mechanisms that are only in part understood. Previous studies suggest that the glucocorticoid-induced TNFR-related protein (GITR), which is preferentially expressed on the surface of Treg cells, potentially provides a signal that abrogates Treg suppression. In this study, we show that a soluble form of mouse GITR ligand (sGITR-L) induces GITR-dependent NF-kappaB activation and blocks in vitro suppression mediated by both resting and preactivated polyclonal and Ag-specific Treg cells.