Group 2 Innate Lymphoid Cells Coordinate Damage Response in the Stomach.

BACKGROUND & AIMS: Severe injury to the lining of the stomach leads to changes in the epithelium (reprogramming) that protect and promote repair of the tissue, including development of spasmolytic polypeptide-expressing metaplasia (SPEM) and tuft and foveolar cell hyperplasia. Acute gastric damage elicits a type-2 inflammatory response that includes production of type-2 cytokines and infiltration by eosinophils and alternatively activated macrophages. Stomachs of mice that lack interleukin 33 (IL33) or interleukin 13 (IL13) did not undergo epithelial reprogramming after drug-induced injury. We investigated the role of group 2 innate lymphoid cells (ILC2s) in gastric epithelial repair. METHODS: Acute gastric injury was induced in C57BL/6J mice (wild-type and RAG1 knockout) by administration of L635. We isolated ILC2s by flow cytometry from stomachs of mice that were and were not given L635 and performed single-cell RNA sequencing. ILC2s were depleted from wild-type and RAG1-knockout mice by administration of anti-CD90.2. We assessed gastric cell lineages, markers of metaplasia, inflammation, and proliferation. Gastric tissue microarrays from patients with gastric adenocarcinoma were analyzed by immunostaining. RESULTS: There was a significant increase in the number of GATA3-positive ILC2s in stomach tissues from wild-type mice after L635-induced damage, but not in stomach tissues from IL33-knockout mice. We characterized a marker signature of gastric mucosal ILC2s and identified a transcription profile of metaplasia-associated ILC2s, which included changes in expression of Il5, Il13, Csf2, Pd1, and Ramp3; these changes were validated by quantitative polymerase chain reaction and immunocytochemistry. Depletion of ILC2s from mice blocked development of metaplasia after L635-induced injury in wild-type and RAG1-knockout mice and prevented foveolar and tuft cell hyperplasia and infiltration or activation of macrophages after injury. Numbers of ILC2s were increased in stomach tissues from patients with SPEM compared with patients with normal corpus mucosa. CONCLUSIONS: In analyses of stomach tissues from mice with gastric tissue damage and patients with SPEM, we found evidence of type 2 inflammation and increased numbers of ILC2s. Our results suggest that ILC2s coordinate the metaplastic response to severe gastric injury.

Adolescents' Intention to Use Long-Acting Reversible Contraception Postpartum.

STUDY OBJECTIVE: Multiparous teens, compared to primiparous teens, are at increased risk for adverse neonatal and maternal outcomes. Long-acting reversible contraception (LARC) is infrequently used among postpartum teens. This study identifies predictors of teens' intentions to use LARC postpartum when it is widely available. METHODS: Colorado teens who were patients during their pregnancy in an adolescent-centered clinic where all common methods of contraception were easily accessible were surveyed in clinic during their third trimester and following delivery regarding life circumstances (relationships, stress, and family function) and intended method of postpartum contraception. Multinomial logistic regression analyses were used to examine predictors of intended postpartum contraceptive method: LARC, non-LARC effective (condoms, birth control pills, shot, patch, or ring), or low-effective method or no contraception (abstinence, no method, or undecided). RESULTS: A total of 1203 patients were enrolled. Greater life stress was associated with greater likelihood of intending to use low-effective contraception versus LARC postpartum. Teens in a longer relationship with their baby's father (versus those never in a relationship with the baby's father) were less likely to intend to use low-effective contraception or non-LARC effective methods and more likely to intend to use LARC postpartum. CONCLUSION: When structural barriers are minimized, non-clinical factors such as relationship context and life stress are most associated with postpartum LARC use intentions. Health care providers can help teen patients obtain the postpartum contraception the patients believe is best by employing developmentally appropriate, person-centered care that is sensitive to life stressors and relationship context.