LAUSR

arietal cell atrophy in the human stomach occurs Palong a continuum of gastric inflammation, atrophy, and then metaplasia, a preneoplastic lesion. In mice, and to a lesser extent in human beings, the best-characterized type of metaplasia is spasmolytic polypeptide-expressing metaplasia. Inflammation in the stomach generally arises in response to autoimmune gastritis or an infection from Helicobacter pylori. Although relatively rare, autoimmune gastritis is known to occur in response to autoantibodies to parietal cell proteins, specifically the a and b subunits of the proton pump Hþ, Kþ-adenosine triphosphatase. New studies from Bockerstett et al used a mouse model of autoimmune gastritis and gastric organoids from the corpus to show a seminal role for cytokines in contrast to the antiparietal cell antibodies (APCAs) in the mechanism of parietal cell death. Transgenic expression of the T cell receptor from a T helper cell 1 (Th1) clone on the BALB/c genetic background mice were genetically engineered to generate antibodies against parietal cells, ultimately triggering gastric atrophy, a mechanism reminiscent of pernicious anemia. Parietal cells produce intrinsic factor, which is required for the absorption of vitamin B12. Therefore, autoimmune destruction of parietal cells reduces B12 levels, causing pernicious anemia. Although APCAs are present in the serum of other autoimmune disorders (eg, type 1 diabetes, vitiligo, autoimmune thyroid disease, and celiac disease), APCAs also are found in H pylori–induced atrophic gastritis. Thus, immunemediated destruction of parietal cells might prove to be the most common mechanism triggering gastric atrophy. Prior studies have focused on Th1-mediated proinflammatory cytokines such as interleukin (IL)1b and tumornecrosis factor-a asmediators of parietal cell atrophy in the setting ofH pylori gastritis. More recently, both Th1 and Th17 immune responses have been implicated. However, the cytokines mediating autoimmune destruction of parietal cells have not been well defined. The findings by Bockerstett et al begin to fill this gap in our understanding by using immune cell analysis to identify a time-dependent increase in IL17A that correlatedwith gastric atrophy andmetaplasia in the TxA23 mice. Bockerstett et al hypothesized that IL17A might exert a direct effect on parietal cells to initiate their demise. They used gastric organoids to show a direct effect of this proinflammatory cytokine on nontransformed gastric cells by treating organoids with IL17A. As a result, primary gastric epithelial cells underwent apoptosis, and complemented the immunohistochemical analysis identifying the IL17 receptor on parietal cells. Taken together, the combination of tissue analysis and organoid cultures linked this IL17 cytokine-ligand interaction to the cascade of caspase-3 activation, culminating in parietal cell apoptosis, ultimately resulting in gastric (corpus) atrophy.