Environmental estrogens, such as bisphenol A (BPA) that is normally used in the manufacture of food and beverage containers, pose increasingly worrisome hazards to human and wildlife health. The adverse effects of BPA are multifaceted; while close attention has been paid to their effect on the immune response system, especially the possible etiology of asthma in children and adults. The underlined mechanism of how BPA influences the biological pathways that alters the normal immune response system is unknown. Here, we report to use various proteomics and biological approaches to identify BPA-targeting proteins and protein pathways in human colonic and CD4+T cell lines and CD4+T cells extracted from mouse spleens. The outcomes of this study revealed that the cellular respiration, phagosome maturation and especially the Sirtuin signaling pathways are among the top canonic or KEGG pathways perturbed by BPA and they are proteome-phenotypic inheritable to multi-generations. Most importantly, a protein palmitoyltransferase, ZDHHC1, was identified as one of the top proteins upregulated by BPA; and further, it was found that ZDHHC1 forms a heterodimer with STING. This novel finding constitutes a mechanistic model better describing how BPA and E2, as well as vitamin D3, are engaged in the immune response of asthma by up-regulating the expression of ZDHHC1 through histone modifications and its down-stream STING signaling pathways.