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Background Children exposed to adversity and toxic stress are at increased risk for poor health across the lifespan, possibly through alterations to immune pathways. Parenting interventions could buffer the effect of adversity on child immune activity. The purpose of this study was to test whether mothers and children who were randomly assigned to a parenting intervention (ATTACH™) had healthier post-intervention immune cell gene expression patterns, as indexed by the Conserved Transcriptional Response to Adversity (CTRA), compared with mothers and children in a wait-list control group. Methods A sample of 20 mother-child dyads were recruited from a domestic violence shelter in Calgary, AB, Canada. The ATTACH™ program is a 10-week psycho-educational intervention that fosters maternal reflective function, i.e. how to understand and respond to mental states. Dyads were randomly assigned to an intervention or wait-list group. Dried blood spots were collected from both groups post-intervention, subjected to RNA sequencing, and assessed for CTRA gene expression using mixed effect linear model analysis. Covariates were age, child sex, maternal race/ethnicity, and maternal medication use. Results In unadjusted models, differences by treatment group were detected, F(1,1794) ​= ​4.26, p ​= ​.039. Mothers and children who completed the ATTACH™ intervention had lower CTRA scores, indicating healthier immune cell gene expression profiles (Mn ​= ​−0.36, SE ​= ​0.17), compared with mothers and children in the wait-list control group (Mn ​= ​0.11, SE ​= ​0.15). Results persisted after controlling for covariates. Discussion ATTACH™ participation predicted healthier immune cell gene expression profiles post-intervention compared with wait-list controls. Parenting interventions could decrease the impact of toxic stress on maternal-child immune health., Highlights • The ATTACH™ program is a reflective function parenting intervention. • The ATTACH™ program predicted healthier immune cell gene expression in children. • The ATTACH™ program predicted healthier immune cell gene expression in mothers. • The ATTACH™ program could protect the health of families escaping domestic violence.