Obesity leads to a switch in subsets of CD4+ T cell in adipose tissue, characterized by an increase in IFNγ producing Th1 cells and a decrease in anti-inflammatory regulatory T (Treg) cells, which impairs systemic insulin sensitivity. What signals these changes is unknown. Herein we demonstrate that genetic deficiency of adipocyte MHCII decreases adipose IFNγ expression and increases adipose Treg abundance in obese mice, leading to reduced obesity-induced adipose inflammation and reduced insulin resistance without affecting weight gain. The preserved insulin sensitivity of high fat diet (HFD)-fed adipocyte-specific MHCII knockout (aMHCII−/−) mice was substantially attenuated by adipose-specific Treg ablation. Adipocytes of aMHCII−/− mice exhibit decreased capacity to stimulate IFNγ production in Th1 cells, whereas HFD-fed IFNγR1−/− mice were more insulin sensitive and had similarly high levels of Tregs in adipose tissue as aMHCII−/− mice. We further show that IFNγ strongly inhibits IL-33 effects to promote adipose Treg proliferation. Our results identify MHCII in adipocyte as a critical determinant of the obesity-induced adipose T cell subset switch and insulin resistance.

Macro-environmental factors, including a patient’s physical and social environment, play a role in cancer risk and progression. Our previous studies show that living in an enriched environment (EE) providing complex stimuli confers an anticancer phenotype in mice mediated in part by a specific neuroendocrine axis, with brain-derived neurotrophic factor (BDNF) as the key brain mediator. Here we investigated how an EE modulated T-cell immunity and its role in the EE-induced anticancer effects. Our data demonstrated that CD8 T cells were required to mediate the anticancer effects of an EE in an orthotropic model of melanoma. In secondary lymphoid tissue (SLT), an EE induced early changes in the phenotype of T-cell populations, characterized by a decrease in the ratio of CD4 T helper to CD8 cytotoxic T lymphocytes (CTLs). Overexpression of hypothalamic BDNF reproduced EE-induced T-cell phenotypes in SLT whereas knockdown of hypothalamic BDNF inhibited EE-induced immune modulation in SLT. Both propranolol and mifepristone blocked the EE-associated modulation of CTLs in SLT suggesting both the sympathetic nervous system and hypothalamic-pituitary-adrenal axis were involved. Our results demonstrated that enhanced anticancer effect of an EE was mediated at least in part through modulation of T-cell immunity and provided support to the emerging concept of manipulating a single gene in the brain to improve cancer immunotherapy.

Environmental and social factors have profound impacts on immune homeostasis. Our work on environmental enrichment (EE) has revealed a novel anti-obesity and anticancer phenotype associated with enhanced activity of CD8+ cytotoxic T lymphocytes in secondary lymphoid tissues. Here we investigated how an EE modulated thymus and thymocyte development. EE decreased thymus mass and cellularity, decreased the double positive thymocyte population, increased the proportion of CD8+ T cells, reduced the CD4:CD8 ratio, and downregulated CD69 expression in T cells. In a model of multiple sclerosis: experimental autoimmune encephalomyelitis (EAE), EE alleviated symptoms, inhibited spinal cord inflammation through regulation of type 1 T-helper cells mediated by glucocorticoid receptor signaling, and prevented EAE-induced thymic disturbance. Our mechanistic studies demonstrated that hypothalamic BDNF activated a hypothalamic-pituitary-adrenal axis mediating the EE’s thymic effects. Our results indicate that a lifestyle intervention links the nervous, endocrine, and adaptive immune system, allowing the body to adapt to internal and external environments.

Creating visual art to teach and learn histologic concepts is uncommon. A pilot visual art program was developed for use in first-year medical student courses that include histology with the hypothesis that creating visual art would subjectively improve the learning process and lead to learner-based personal incorporation of art into in future learning. Prior to the term, volunteers (n=25) were recruited from 89 first-year medical students. The volunteer group was given art supplies and encouraged to draw histologic images in a free-form setting without restrictions. The control group (n=64) consisted of non-volunteers. Pre- and post-term surveys were distributed to all students, of which 72% and 45% completed the surveys, respectively. Regardless of participation, a majority of students viewed art as a valuable tool to learn medicine prior to and following the term (73% and 82.5%, respectively), however less than half admitted to using art to learn medical concepts (42% and 40%, respectively). In the post-term survey, a higher percentage of students in the experimental group stated they will use art to learn medical concepts in the future (75% vs 40.6%). Most students considered art to be a valuable resource to learn concepts in medicine, including all the students who participated in the art program. Based on the number of students who reported intent to change behavior, the initial hypothesis is supported. Many students favor incorporation of visual art into medical education, we believe that creating visual art may be a worthwhile adjunct tool for histology education.

Objective: Previous studies examining changes in central sleep apnea (CSA) following adenotonsillectomy (T&A) performed for obstructive sleep apnea (OSA) in children have been limited by sample size and analysis of only certain populations. The aim of this study was to determine whether CSA improves following T&A and what factors mediate this change.Methods: This was a retrospective case series from 1994 to 2020 of children undergoing primary T&A for OSA (obstructive apnea-hypopnea index ≥1) with CSA (central apnea index [CAI] ≥1) and preoperative and postoperative polysomnograms within 12 months of T&A. Polysomnograms were analyzed for improvement in CSA, defined as: 1) if preoperative CAI >5, a postoperative CAI <5; or 2) if preoperative CAI <5, a postoperative CAI <1.Results: One hundred twenty-three patients were included. Median age was 5.5 years (interquartile range, 2.9-8.4). Most patients were overweight/obese (58.5%). Nineteen (15.4%) had a syndromic condition. Preoperative CAI was ≥5 in 21 (17.1%) patients. CAI significantly decreased following T&A (preoperative 2.1, postoperative 0.4; P < .001). Thirty-two (26.0%) patients had CSA postoperatively. Improvement in the microarousal index and older age were significantly associated with improvement in CSA.Conclusions: T&A led to resolution of CSA in most children with OSA. Improvement in the microarousal index was associated with improvement in CAI, suggesting that preoperative central apneas may be postarousal and thus resolve following T&A.