In the nearly 100 years since the discovery of therapeutic insulin significant research efforts have been directed at finding the underlying cause of type 1 diabetes (T1D) and developing a “cure” for the disease. become extraordinarily hard to traverse from your perspective of investigators. As a result there is an increasing LTX-315 LTX-315 pressure toward overall performance of what might be considered “safe” research where the aim is to affirm existing dogmas rather than to pioneer efforts involving unconventional thought. Psychologists refer to this practice as “observational bias” while cartoonists label the process the “streetlight effect.” In this Perspective we consider notions in T1D research that should be subject to strong question and provide additional concepts many somewhat orphan to research efforts whose LTX-315 investigation could lead to a means for truly identifying the cause of and a cure for T1D. Rabbit Polyclonal to FSHR. The Streetlight Effect The historical origins for the notion of the “streetlight effect” are subject to considerable argument (https://en.wikipedia.org/wiki/Streetlight_effect). Regardless perhaps its most famous use was an application within the comic strip (1) (Fig. 1). The narrative ascribed to this streetlight effect conveyed a message: At least eight features be they pathogenic immunologic physiologic or metabolic appear to be misunderstood or underappreciated in T1D. The features explained within these domains … An additional largely neglected immune cell subset in T1D is usually γ-δ LTX-315 (γδ) T lymphocytes. In the NOD mouse interleukin-17+ γδ T cells are essential effectors in T1D development (13) while in humans data are scarce aged and contradictory (examined in 14). This example of γ-δ T cells is usually typical of research areas that address cells rarely circulating and largely found in the tissue. Thus the new availability of relevant tissues from patients with T1D and control subjects such as those emanating from your Network for Pancreatic Organ Donors with Diabetes (nPOD) (15) should foster research aimed at not only confirming aged hypotheses but also testing new suggestions. Space constraints limit us from discussing the full cadre of potential constituents of inflammation and the LTX-315 innate and adaptive immune responses that likely contribute to the disorder’s pathogenesis. Nonetheless their evaluation largely resides outside of the streetlight and hence represents an important venue for expanded exploration. Streetlight.