Erienced sustained weight loss (Figure 1A) along with a larger variety of BAL total cells (Figure 1C), with predominance of neutrophils (Figure 1D). In addition, the proportion of alveolar cells showed a greater percentage of neutrophils in addition to a reduce percentage of macrophages within the male host by day six soon after PNA (Supplemental Figure 1; supplemental material out there on the web with this short article; https://doi.org/10.1172/jci.insight.133251DS1). The lung compartment profile of sustained inflammatory cells was similar for the alveolar compartment (Figure 1, G and H). The amount of alveolar macrophages and lymphocytes was related at all intervals after injury in male mice compared with female mice (Figure 1, E and F). Analysis of sex variations in BAL cytokines at more than time in the course of PNA demonstrated comparable BAL proinflammatory cytokine profiles in both sexes at day 2 ofinsight.jci.org https://doi.org/10.1172/jci.insight.133251RESEARCH ARTICLEFigure 1. Female mice show enhanced resolution of pneumonia. Age-matched WT male and female mice were challenged with intratracheal S. pneumoniae (4 106 CFU/mouse) and followed over time. Lung injury parameters had been assessed on days 0, two, and six. (A) Body weight over time relative to baseline at day 0. (B ) BAL total protein (B), BAL total cell count (C), and BAL differential cell counts (D ) have been determined over time in female and male WT mice right after intratracheal S. pneumoniae. (G and H) Total lung total cell counts and lung neutrophil counts had been determined in female and male mice right after intratracheal S. pneumoniae. Two-way ANOVA was used. n = 6 per group per time point. P 0.05. Values are reported as mean SEM.PNA. In contrast, by day 6, female mice had CXCR7 Activator Formulation considerably reduced BAL IFN-, IL-12, IL-6, and TNF- when compared with male mice (Supplemental Figure two). These information recommend that female mice, in contrast to male mice, displayed enhanced resolution of related lung inflammation immediately after S. pneumoniae. Alveolar and lung Tregs increased in female mice with resolving PNA. We next examined baseline Treg numbers and function in male and female mice in alveolar and lung compartments. At baseline, no differences in BAL and lung cell counts were observed. Lung Treg numbers had been related in each sexes at baseline (Supplemental Figure 3). Baseline expression of Treg glucocorticoid-induced TNFRrelated protein (GITR) in the lungs of female mice was higher than that in male mice, although both sexes had similar Treg expression for Foxp3, CD25, and GATA3 (Supplemental Figure 3). Throughout resolution, S. pneumoniae njured female mice displayed a larger absolute fold improve inside the variety of alveolar (Figure 2A) and lung Tregs (Figure 2B) compared with their male counterparts. The proportion of Tregs in alveolar and lung compartments was considerably elevated compared with that in male mice at day six (Figure 2, C and D). Notably, Foxp3 (Figure 2E) and Ki-67 (Figure 2F) expression was greater in female mice than in male mice during resolution, indicating an enhanced proliferative state. Treg GATA3 expression was CYP3 Activator drug equivalent in male and female mice (Figure 2G). Consistent with enhanced lung injury resolution, female mice demonstrated improved Treg numbers in both the lung and alveolar compartment. Further, markers of suppressive phenotype were enhanced in female Tregs relative to male Tregs. Exogenous estrogen enhanced the suppressive phenotype of Tregs. To decide the effect of exogenous E2 on Tregs, we cultured the CD4+CD25+ (Tregs, 85 Foxp3+).