Bronchoalveolar Tregs are associated with duration of mechanical ventilation in acute respiratory distress syndrome.

BACKGROUND: Foxp3+ regulatory T cells (Tregs) play essential roles in immune homeostasis and repair of damaged lung tissue. We hypothesized that patients whose lung injury resolves quickly, as measured by time to liberation from mechanical ventilation, have a higher percentage of Tregs amongst CD4+ T cells in either airway, bronchoalveolar lavage (BAL) or peripheral blood samples. METHODS: We prospectively enrolled patients with ARDS requiring mechanical ventilation and collected serial samples, the first within 72 h of ARDS diagnosis (day 0) and the second 48-96 h later (day 3). We analyzed immune cell populations and cytokines in BAL, tracheal aspirates and peripheral blood, as well as cytokines in plasma, obtained at the time of bronchoscopy. The study cohort was divided into fast resolvers (FR; n = 8) and slow resolvers (SR; n = 5), based on the median number of days until first extubation for all participants (n = 13). The primary measure was the percentage of CD4+ T cells that were Tregs. RESULTS: The BAL of FR contained more Tregs than SR. This finding did not extend to Tregs in tracheal aspirates or blood. BAL Tregs expressed more of the full-length FOXP3 than a splice variant missing exon 2 compared to Tregs in simultaneously obtained peripheral blood. CONCLUSION: Tregs are present in the bronchoalveolar space during ARDS. A greater percentage of CD4+ cells were Tregs in the BAL of FR than SR. Tregs may play a role in the resolution of ARDS, and enhancing their numbers or functions may be a therapeutic target.

Sending a Signal: Evaluating the Impact of Program and Geographic Preference Signaling on the Internal Medicine Residency Match.

Background For over a decade, the number of residency applications has surged, a trend known as "application inflation." COVID-19 further intensified this trend, leading the Association of American Medical Colleges (AAMC) to address the issue by introducing a supplemental application in the 2021-2022 cycle, allowing programs to identify applicants with a connection to their program or geographic region. For the 2022-2023 cycle, the number of program signals increased from five to seven. The impact of the supplemental application and the increase in signals on the likelihood of an applicant matching with a program has yet to be evaluated. Methods This retrospective cohort study evaluated the impact of program signaling and geographic preference on the matching likelihood in our internal medicine residency program. Data from MyERAS® and the Supplemental Application for 640 applicants who applied to our large, urban, university-based program in the Southeastern United States during the 2020-2021 and 2022-2023 application cycles were included. Using univariate and multivariate analysis, we examined the correlation between program signal, geographic preference, and final match location. Results Applicants who sent a program signal had nearly three-fold higher odds of matching with our program. Geographic preference was numerically but not statistically associated with higher odds of matching. Both signaling a preference for matching with a program in an urban environment and couples matching correlated with decreased odds of matching with our program. Geography was an important predictor of match location as residing in our AAMC geographic region, our four-state area, and our specific state had increased odds of matching with our program. Conclusions Signaling our program was associated with increased odds of matching with our program. Geographic preferences were less predictive of a match with our program; however, they did predict the likelihood of a match at a program within that region. Future studies are needed to ensure external validity.

Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI.

Recovery from acute lung injury (ALI) is an active process. Foxp3+ Tregs contribute to recovery from ALI through modulating immune responses and enhancing alveolar epithelial proliferation and tissue repair. The current study investigates Treg transcriptional profiles during resolution of ALI in mice. Tregs from either lung or splenic tissue were isolated from uninjured mice or mice recovering from ALI and then examined for differential gene expression between these conditions. In mice with ALI, Tregs isolated from the lungs had hundreds of differentially expressed transcripts compared with those from the spleen, indicating that organ specificity and microenvironment are critical in Treg function. These regulated transcripts suggest which intracellular signaling pathways modulate Treg behavior. Interestingly, several transcripts having no prior recognized function in Tregs were differentially expressed by lung Tregs during resolution. Further investigation into 2 identified transcripts, Mmp12 and Sik1, revealed that Treg-specific expression of each plays a role in Treg-promoted ALI resolution. This study provides potentially novel information describing the signals that may expand resident Tregs, recruit or retain them to the lung during ALI, and modulate their function. The results provide insight into both tissue- and immune microenvironment-specific transcriptional differences through which Tregs direct their effects.