Erienced sustained weight reduction (Figure 1A) as well as a larger quantity of BAL total cells (Figure 1C), with predominance of neutrophils (Figure 1D). Furthermore, the proportion of alveolar cells showed a greater percentage of neutrophils and a lower percentage of macrophages within the male host by day six after PNA (Supplemental Figure 1; supplemental material offered on line with this short article; https://doi.org/10.1172/jci.insight.133251DS1). The lung compartment profile of sustained inflammatory cells was related to the alveolar compartment (Figure 1, G and H). The amount of alveolar macrophages and lymphocytes was comparable at all intervals soon after injury in male mice compared with IL-17 Inhibitor Accession female mice (Figure 1, E and F). Analysis of sex variations in BAL cytokines at over time through PNA demonstrated equivalent BAL proinflammatory cytokine profiles in each sexes at day two ofinsight.jci.org https://doi.org/10.1172/jci.insight.133251RESEARCH ARTICLEFigure 1. Female mice show enhanced resolution of pneumonia. IL-23 Inhibitor medchemexpress Age-matched WT male and female mice were challenged with intratracheal S. pneumoniae (4 106 CFU/mouse) and followed more than time. Lung injury parameters have been assessed on days 0, two, and 6. (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 more than time in female and male WT mice soon after intratracheal S. pneumoniae. (G and H) Total lung total cell counts and lung neutrophil counts have been determined in female and male mice after intratracheal S. pneumoniae. Two-way ANOVA was utilized. n = 6 per group per time point. P 0.05. Values are reported as imply SEM.PNA. In contrast, by day six, female mice had substantially reduced BAL IFN-, IL-12, IL-6, and TNF- when compared with male mice (Supplemental Figure two). These data suggest that female mice, in contrast to male mice, displayed enhanced resolution of equivalent lung inflammation just after S. pneumoniae. Alveolar and lung Tregs elevated 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 variations in BAL and lung cell counts had been observed. Lung Treg numbers had been comparable 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, when both sexes had related Treg expression for Foxp3, CD25, and GATA3 (Supplemental Figure three). In the course of resolution, S. pneumoniae njured female mice displayed a larger absolute fold raise within the quantity 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 higher in female mice than in male mice through resolution, indicating an enhanced proliferative state. Treg GATA3 expression was similar in male and female mice (Figure 2G). Constant with enhanced lung injury resolution, female mice demonstrated elevated Treg numbers in each the lung and alveolar compartment. Additional, markers of suppressive phenotype had been enhanced in female Tregs relative to male Tregs. Exogenous estrogen enhanced the suppressive phenotype of Tregs. To establish the effect of exogenous E2 on Tregs, we cultured the CD4+CD25+ (Tregs, 85 Foxp3+).