The transcriptional repressor ID2 supports natural killer cell maturation by controlling TCF1 amplitude

Gaining a mechanistic understanding of the expansion and maturation program of natural killer (NK) cells will provide opportunities for harnessing their inflammation-inducing and oncolytic capacity for therapeutic purposes. Here, we demonstrated that ID2, a transcriptional regulatory protein constitutively expressed in NK cells, supports NK cell effector maturation by controlling the amplitude and temporal dynamics of the transcription factor TCF1. TCF1 promotes immature NK cell expansion and restrains differentiation. The increased TCF1 expression in ID2-deficient NK cells arrests their maturation and alters cell surface receptor expression. Moreover, TCF1 limits NK cell functions, such as cytokine-induced IFN-gamma production and the ability to clear metastatic melanoma in ID2-deficient NK cells. Our data demonstrate that ID2 sets a threshold for TCF1 during NK cell development, thus controlling the balance of immature and terminally differentiated cells that support future NK cell responses.Funding Agencies|National Institutes of Allergy and Infectious DiseasesUnited States Department of Health &amp; Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Allergy &amp; Infectious Diseases (NIAID) [R01 AI106352]; National Cancer InstituteUnited States Department of Health &amp; Human ServicesNational Institutes of Health (NIH) - USANIH National Cancer Institute (NCI) [P30 CA014599]</p

Mortality and PICU hospitalization among pediatric gunshot wound victims in Chicago

Firearm injury accounts for significant morbidity with high mortality among children admitted to the PICU. Understanding risk factors for PICU admission is an important step toward developing prevention and intervention strategies to minimize the burden of pediatric gunshot wound (GSW) injury. Objectives: The primary objective of this study was to characterize outcomes and the likelihood of PICU admission among children with GSWs. Design setting and participants: Retrospective cohort study of GSW patients 0-18 years old evaluated at the University of Chicago Comer Children\u27s Hospital Pediatric Trauma Center from 2010 to 2017. Main outcomes and measures: Demographic and injury severity measures were acquired from an institutional database. We describe mortality and hospitalization characteristics for the cohort. We used logistic regression models to test the association between PICU admission and patient characteristics. Results: During the 8-year study period, 294 children experienced GSWs. We did not observe trends in overall mortality over time, but mortality for children with GSWs was higher than all-cause PICU mortality. Children 0-6 years old experienced longer hospitalizations compared with children 13-16 years old (5 vs 3 d; p = 0.04) and greater frequency of PICU admission (83.3% vs 52.9%; p = 0.001). Adjusting for severity of illness, children less than 7 years old were four-fold more likely to be admitted to the PICU than children 13-16 years old (aOR range, 3.9-4.6). Conclusions and relevance: Despite declines in pediatric firearm mortality across the United States, mortality did not decrease over time in our cohort and was higher than all-cause PICU mortality. Younger children with GSWs experience longer hospitalizations and require PICU care more often than older children. Our findings suggest that the youngest victims of firearm-related injury may be particularly at-risk of the long-term sequelae of critical illness and injury