Sort by
Abstract P3165: Spectrin-based Regulation Of Exosome Secretion In Cardiac Fibroblasts

Cardiac fibroblasts (CFs) not only modulate the extracellular matrix under physiological conditions, but also have the ability to sense local injury and respond with a phenotypic change and increased paracrine communication to distal cells. While a myriad of studies have focused on identifying the paracrine signals involved in recruitment and activation of CFs, the manner by which CF paracrine communication networks are tuned in response to chronic stress remains unclear. Previously, our lab found that stress-induced loss of the cytoskeletal protein, β IV -spectrin, regulates the CF phenotype and fibrosis. Therefore, we hypothesized that degradation of β IV -spectrin is a critical step in stress-induced communication involved in recruitment of distal CFs. In this study, we first collected conditioned media from WT and β IV -spectrin deficient (qv 4J ) CFs to test the effects on quiescent WT CFs. We found that the CFs treated with qv 4J -conditioned media showed increased proliferation and compaction rates, as well as altered gene expression in the recipient cells compared to those treated with WT-conditioned media. To further explore the role of β IV -spectrin in paracrine signaling, we isolated exosomes from WT- and qv 4J -conditioned media. We found that loss of β IV -spectrin in CFs resulted in an increased concentration of exosomes in conditioned media, that also induced increased proliferation in quiescent CFs. Furthermore, we found that genetic mice expressing degradation-resistant β IV -spectrin ( qv 3J mice) showed impaired CF recruitment and activation following myocardial infarction (MI) together with increased mortality and impaired fibrotic remodeling compared to WT. Finally, we demonstrate that exosomes from a WT-MI heart can improve fibrotic remodeling in qv 3J mice following MI. Our work identifies a novel role of the spectrin-based pathway in facilitating long-range communication in response to chronic stress.

Relevant
Couple Religiosity, Male Headship, Intimate Partner Violence, and Infidelity

Background The research literature finds a positive relationship between couple religiosity and relationship quality, but because public discourse highlights religious victims of domestic violence, we questioned whether couple religiosity prevents negative relationship outcomes as well as it promotes positive ones. Purpose This article compares rates of intimate partner violence (IPV) and infidelity among couples with different levels of religious commitment. We further interrogated whether the belief that the man is the head of the household increased couples’ risk of IPV or infidelity. Methods We used Global Family and Gender Survey data from eleven countries. This was an online survey of adults ages 18 to 50 that used a representative panel for the United States, but used opt-in panels in Australia, France, Ireland, United Kingdom, Canada, Argentina, Chile, Colombia, Mexico, and Peru. We limited our analytic sample to the 9920 men and women in heterosexual relationships (6791 married and 3128 cohabiting). We also analyzed the United States probability sample separately from our pooled sample. Results Couples with nominal or unequal religiosity ( less/mixed religious couples) had higher rates of infidelity than either highly religious couples or couples in which neither partner exhibited much religiosity ( shared secular couples). Infidelity was generally similar between highly religious couples and shared secular couples, but in the US women in highly religious couples did cheat less. We found no differences in IPV—measured by both women's reports of victimization and men's reports of perpetration—according to couple religiosity. Further, the belief that the man is the head of the household did not influence couples’ risk of either IPV or infidelity across the entire sample. In Latin America, however, patriarchal men in shared secular couples perpetrated IPV significantly more often than their egalitarian or more religious counterparts. Conclusions and Implications Our Latin American evidence hints that patriarchy may be a more dangerous ideology for secular couples than for religious couples. Our more general conclusion is that even though negative relationship outcomes are not more common among religious couples, the resources religious traditions have at their disposal to discourage violence within intimate partnerships seem tragically underutilized.

Relevant
Phenotype, effector function, and tissue localization of PD-1-expressing human follicular helper T cell subsets

BackgroundIt is well established that PD-1 is expressed by follicular T cells but its function in regulation of human T helper cells has been unclear. We investigated the expression modality and function of PD-1 expressed by human T cells specialized in helping B cells.ResultsWe found that PD-1-expressing T cells are heterogeneous in PD-1 expression. We identified three different PD-1-expressing memory T cell subsets (i.e. PD-1low (+), PD-1medium (++), and PD-1high (+++) cells). PD-1+++ T cells expressed CXCR5 and CXCR4 and were localized in the rim of germinal centers. PD-1+ or PD-1++ cells expressed CCR7 and were present mainly in the T cell area or other parts of the B cell follicles. Utilizing a novel antigen density-dependent magnetic sorting (ADD-MS) method, we isolated the three T cell subsets for functional characterization. The germinal center-located PD-1+++ T cells were most efficient in helping B cells and in producing IL-21 and CXCL13. Other PD-1-expressing T cells, enriched with Th1 and Th17 cells, were less efficient than PD-1+++ T cells in these capacities. PD-1+++ T cells highly expressed Ki-67 and therefore appear active in cell activation and proliferation in vivo. IL-2 is a cytokine important for proliferation and survival of the PD-1+++ T cells. In contrast, IL-21, while a major effector cytokine produced by the PD-1-expressing T helper cells, had no function in generation, survival, or proliferation of the PD-1-expressing helper T cells at least in vitro. PD-1 triggering has a suppressive effect on the proliferation and B cell-helping function of PD-1+++ germinal center T cells.ConclusionOur results revealed the phenotype and effector function of PD-1-expressing T helper cell subsets and indicate that PD-1 restrains the B cell-helping function of germinal center-localized T cells to prevent excessive antibody response.

Open Access
Relevant