The impact of Transposable Elements (TEs) in health and disease has been cemented by mounting evidence. Among the multifaceted co-opted functions of these elements is their involvement in immunity. Here, following on from previous work where we showed that the loss of the epigenetic complex - the Human Silencing Hub (HUSH) – can lead to an interferon (IFN) cascade downstream of the dsRNA sensor MDA5, we sought to shed light on the role of Long INterspersed Elements-1 (LINE-1) in nucleic acid sensing. To this end we employed a short hairpin RNA, selected from a panel of shRNAs targeting LINE-1 subfamilies, which is effective at blocking the type I interferon response induced upon inactivation of the chromodomain-containing component of HUSH, MPP8. By performing total RNA-sequencing of IFN reporter cells expressing this hairpin together with shMPP8, we could computationally identify self-RNAs that are candidates for inducing a type I IFN response and which may be involved in autoimmunity. Thus, our results bring us one step closer to disentangling the intricate role of LINE1s in immunity.