Mariana Rodrigues , Jemar R. Bather , Adolfo G. Cuevas
{"title":"Differential associations between relationship stressors and natural killer cell gene expression by race/ethnicity and sex among older U.S. adults","authors":"Mariana Rodrigues , Jemar R. Bather , Adolfo G. Cuevas","doi":"10.1016/j.bbi.2025.106116","DOIUrl":null,"url":null,"abstract":"<div><div>Close interpersonal relationships can shape health, in part, through immune-related biological pathways. While chronic relational stress has been linked to inflammation and immune dysregulation, little is known about how such stressors relate to transcriptional markers of innate immune activity. As such, we investigated whether multiple forms of relationship stress were associated with altered expression of two genes related to natural killer cell function, <em>FCGR3A</em> and <em>NCAM1,</em> and whether these associations varied by sex or race/ethnicity. Data were drawn from the Midlife in the United States study, a population-based sample of midlife adults (n = 1,215) who provided whole-transcriptome RNA sequencing data and completed validated relationship stress measures. Covariate-adjusted linear mixed effects models, which included random intercepts for study site, quantified the associations of each stress domain z-score with log2(<em>FCGR3A</em>) and log2(<em>NCAM1</em>), and tested for moderation by sex and race/ethnicity. While males maintained relatively stable expression across stress domains, females showed significant positive associations between <em>FCGR3A</em> expression and both marital risk and spouse/partner strain. For participants in the non-Hispanic Other group, higher friend and cumulative strain was significantly associated with elevated <em>FCGR3A</em> expression. This group also exhibited significant <em>NCAM1</em> upregulation in response to family, friend, and cumulative strain. In contrast, Hispanic participants showed a non-significant trend toward <em>NCAM1</em> downregulation under relationship strain, but not significant changes in <em>FCGR3A</em>. These findings suggest that relationship stress may be differentially biologically embedded through changes in innate immune gene expression across demographic groups, highlighting the importance of social context in shaping transcriptional markers of immune function. Further research is needed to clarify whether these patterns confer adaptive immune readiness or contribute to long-term immune dysregulation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106116"},"PeriodicalIF":7.6000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0889159125003587","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Close interpersonal relationships can shape health, in part, through immune-related biological pathways. While chronic relational stress has been linked to inflammation and immune dysregulation, little is known about how such stressors relate to transcriptional markers of innate immune activity. As such, we investigated whether multiple forms of relationship stress were associated with altered expression of two genes related to natural killer cell function, FCGR3A and NCAM1, and whether these associations varied by sex or race/ethnicity. Data were drawn from the Midlife in the United States study, a population-based sample of midlife adults (n = 1,215) who provided whole-transcriptome RNA sequencing data and completed validated relationship stress measures. Covariate-adjusted linear mixed effects models, which included random intercepts for study site, quantified the associations of each stress domain z-score with log2(FCGR3A) and log2(NCAM1), and tested for moderation by sex and race/ethnicity. While males maintained relatively stable expression across stress domains, females showed significant positive associations between FCGR3A expression and both marital risk and spouse/partner strain. For participants in the non-Hispanic Other group, higher friend and cumulative strain was significantly associated with elevated FCGR3A expression. This group also exhibited significant NCAM1 upregulation in response to family, friend, and cumulative strain. In contrast, Hispanic participants showed a non-significant trend toward NCAM1 downregulation under relationship strain, but not significant changes in FCGR3A. These findings suggest that relationship stress may be differentially biologically embedded through changes in innate immune gene expression across demographic groups, highlighting the importance of social context in shaping transcriptional markers of immune function. Further research is needed to clarify whether these patterns confer adaptive immune readiness or contribute to long-term immune dysregulation.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.