CD56 Expression Marks Human Group 2 Innate Lymphoid Cell Divergence from a Shared NK Cell and Group 3 Innate Lymphoid Cell Developmental Pathway.

According to the established model of murine innate lymphoid cell (ILC) development, helper ILCs develop separately from natural killer (NK) cells. However, it is unclear how helper ILCs and NK cells develop in humans. Here we elucidated key steps of NK cell, ILC2, and ILC3 development within human tonsils using ex vivo molecular and functional profiling and lineage differentiation assays. We demonstrated that while tonsillar NK cells, ILC2s, and ILC3s originated from a common CD34-CD117+ ILC precursor pool, final steps of ILC2 development deviated independently and became mutually exclusive from those of NK cells and ILC3s, whose developmental pathways overlapped. Moreover, we identified a CD34-CD117+ ILC precursor population that expressed CD56 and gave rise to NK cells and ILC3s but not to ILC2s. These data support a model of human ILC development distinct from the mouse, whereby human NK cells and ILC3s share a common developmental pathway separate from ILC2s.

Vasomotor symptoms and their links to cardiovascular disease risk.

Hot flashes and night sweats, also known as vasomotor symptoms (VMS), are common and bothersome symptoms of the menopause transition. In addition to negatively impacting quality of life, VMS have been associated with multiple indicators of cardiovascular disease (CVD) risk, including an unfavorable CVD risk factor profile, increased subclinical CVD, and elevated risk of CVD events. Several facets of VMS have been associated with CVD risk, including the frequency, timing, duration, and severity of VMS. VMS may signify poor or degrading cardiovascular health among midlife women and indicate women who warrant focused CVD prevention efforts.

Childhood Maltreatment and Arterial Stiffness Among Midlife Women.

Background Childhood maltreatment has been associated with arterial stiffness. This relationship has not been examined specifically among women at midlife, a time of increased arterial stiffness in women. This study tested whether childhood maltreatment is associated with arterial stiffness among a cohort of midlife women. Methods and Results A total of 162 nonsmoking perimenopausal and postmenopausal women free of clinical cardiovascular disease (mean age, 54 years; 72% White race, 23% Black race, and 5% Asian/Pacific Islander or Mixed race) completed the Child Trauma Questionnaire at baseline. At a follow-up visit 5 years later, blood pressure and carotid-femoral pulse wave velocity (a measure of arterial stiffness) were assessed. Relationships between childhood maltreatment and carotid-femoral pulse wave velocity were tested in linear regression models, adjusting for time between visits, age, race and ethnicity, education, body mass index, heart rate, hypertension medication, and diastolic blood pressure. Seventy-one women (44% of the sample) met criteria for a history of childhood maltreatment. Women with a history of childhood maltreatment had higher carotid-femoral pulse wave velocity (B [SE]=0.47 [0.21]; P=0.03) than women without this history, controlling for time between visits, age, race and ethnicity, education, body mass index, heart rate, hypertension medication, and diastolic blood pressure. Conclusions Among these midlife women, childhood maltreatment was associated with arterial stiffness, highlighting the potential long-term cardiovascular implications of childhood maltreatment.

The relationship of trauma exposure to heart rate variability during wake and sleep in midlife women.

Traumatic experiences are common and linked to cardiovascular disease (CVD) risk, yet the mechanisms underlying these relationships is less well understood. Few studies have examined trauma exposure and its relation to autonomic influence over cardiac function, a potential pathway linking trauma exposure to CVD risk. Investigating autonomic influence over cardiac function during both wake and sleep is critical, given particular links of sleep autonomic function to cardiovascular health. Among midlife women, we tested whether trauma exposure would be related to lower high frequency heart rate variability (HF-HRV), an index of vagal influence over cardiac function, during wake and sleep. Three hundred and one nonsmoking midlife women completed physical measures, a 24-hr electrocardiogram, actigraphy sleep measurement, and questionnaires about trauma (Brief Trauma Questionnaire), childhood abuse (Child Trauma Questionnaire [CTQ]), mood, demographics, and medical/psychiatric history. Relations between trauma and HF-HRV were assessed in linear mixed effects models adjusting for covariates (age, race, education, body mass index, blood pressure, psychiatric history, medication use, sleep, mood, childhood abuse history). Results indicated that most women had experienced trauma. Any trauma exposure as well as a greater number of traumatic experiences were associated with lower HF-HRV during wake and particularly during sleep. Relations were not accounted for by covariates. Among midlife women, trauma exposure was related to lower HF-HRV during wake and sleep. Trauma may have an important impact on vagal influence over the heart, particularly during sleep. Decreased vagal influence over cardiac function may be a key mechanism by which trauma is associated with CVD risk.

Childhood abuse and vasomotor symptoms among midlife women.

OBJECTIVE: Childhood maltreatment is related to adverse health outcomes. However, the relation of childhood maltreatment to the menopause transition-a universal transition for women often accompanied by troubling symptoms such as vasomotor symptoms-is relatively underexplored. This study tested whether childhood abuse and neglect are associated with menopausal vasomotor symptoms, utilizing both physiologic and prospective self-report measures of vasomotor symptoms. METHODS: In all, 295 nonsmoking perimenopausal and postmenopausal women aged 40 to 60 years with and without vasomotor symptoms completed psychosocial measures, including the Child Trauma Questionnaire, ambulatory physiologic (sternal skin conductance) and self-report measurement of vasomotor symptoms during wake and sleep, and actigraphy measurement of sleep. Relationships between childhood abuse/neglect and vasomotor symptoms during wake and sleep were tested in linear regression models controlling for demographics, body mass index, and menopause stage. RESULTS: 44% of the sample reported abuse or neglect during childhood. Among women reporting vasomotor symptoms, childhood sexual or physical abuse was associated with more frequent physiologically-recorded vasomotor symptoms during sleep (sexual abuse: b [SE] = 1.45 [0.52], P = 0.006; physical abuse: b [SE] = 0.97 [0.47], P = 0.03) in multivariable models. Among these women, women with a physical or sexual abuse history had approximately 1.5 to 2-fold the number of sleep vasomotor symptoms than women without this history. CONCLUSIONS: Childhood abuse is associated with more frequent physiologically-detected vasomotor symptoms during sleep.