Intensive study of interleukin-4 for more than three decades has revealed multiple functions of this cytokine in diverse processes. Nevertheless, the wide distribution of Interleukin-4 suggests the possibility of unexplored roles. Indeed, in here we present a novel role of IL-4 for the maintenance of different populations of stromal cells in peripheral lymph nodes at homeostasis and describe a role of IL-4 in the expansion of these stromal populations following antigen challenge. In consequence, IL-4 is fundamental for mounting an appropriate humoral response to a primary immunization, and absence of this cytokine is detrimental for the development of a Type 2 response. Furthermore, we describe the role of IL-4 in the immune responses of offspring antenatally exposed to <i>Schistosoma mansoni</i>antigens. Diminished IL-4 production is linked to reduced cellular T and B cells responses in offspring derived from infected mothers, which is of critical relevance to understand vaccination failure. Finally, we describe the protective role of Schistosomiasis infection in atherosclerosis and propose possible mechanism that helps explain the athero-protection. This will contribute to the discovery of novel pathways inducing protection from cardiovascular disease and help to identify possible targets for novel treatments