Estrogen regulates sex-specific localization of regulatory T cells in adipose tissue of obese female mice
PLOS ONE
Authors: Ishikawa, Akari; Wada, Tsutomu; Nishimura, Sanshiro; Ito, Tetsuo; Okekawa, Akira; Onogi, Yasuhiro; Watanabe, Eri; Sameshima, Azusa; Tanaka, Tomoko; Tsuneki, Hiroshi; Saito, Shigeru; Sasaoka, Toshiyasu
Abstract
Regulatory T cells (Treg) play essential roles in maintaining immune homeostasis. Resident Treg in visceral adipose tissue (VAT-Treg) decrease in male obese mice, which leads to the development of obesity-associated chronic inflammations and insulin resistance. Although gender differences in immune responses have been reported, the effects of the difference in metabolic environment on VAT-Treg are unclear. We investigated the localization of VAT-Treg in female mice in comparison with that in male mice. On a high-fat diet (HFD), VAT-Treg decreased in male mice but increased in female mice. The increase was abolished in ovariectomized and HFD-fed mice, but was restored by estrogen supplementation. The IL33 receptor ST2, which is important for the localization and maturation of VAT-Treg in males, was reduced in CD4(+)CD25(+) T cells isolated from gonadal fat of obese mice of both genders, suggesting that a different system exists for VAT-Treg localization in females. Extensive analysis of chemokine expression in gonadal fat and adipose CD4(+)CD25(+)T cells revealed several chemokine signals related to female-specific VAT-Treg accumulation such as CCL24, CCR6, and CXCR3. Taken together, the current study demonstrated sexual dimorphism in VAT-Treg localization in obese mice. Estrogen may attenuate obesity-associated chronic inflammation partly through altering chemokine-related VAT-Treg localization in females.
Bronchiolitis and recurrent wheezing are distinguished by type 2 innate lymphoid cells and immune response
PEDIATRIC ALLERGY AND IMMUNOLOGY
Authors: Sastre, Beatriz; Luz Garcia-Garcia, Maria; Antonio Canas, Jose; Calvo, Cristina; Manuel Rodrigo-Munoz, Jose; Casas, Inmaculada; Mahillo-Fernandez, Ignacio; del Pozo, Victoria
Abstract
Background Recurrent wheezing (RW) is frequently developed in infants that have suffered bronchiolitis (BCH) during first months of life, but the immune mechanism underlying is not clear. The goal was to analyze the innate immune response that characterizes BCH and RW. Methods Ninety-eight and seventy hospitalized infants with BCH or RW diagnosis, respectively, were included. Nasopharyngeal aspirate (NPA) was processed. Cellular pellet was employed to evaluate type 2 innate lymphoid cells (ILC2) by flow cytometry and mRNA expression assays by semi-quantitative real-time PCR (qRT-PCR). In supernatant, twenty-seven pro-inflammatory and immunomodulatory factors, as well as lipid mediators and nitrites, were evaluated by ELISA and Luminex. Results Bronchiolitis patients showed higher ILC2 percentage compared with RW (P < .05). Also, ST2(+)/ILC2 percentage was higher in the BCH group than in the RW group (P < .01).TLR3,IL33,IFNG,IL10, andFLGmRNA levels were significantly increased in BCH vs RW (P < .05). In supernatant, no significant differences were reached, observing similar levels of parameters linked to vascular damage, monocyte activation, and fibroblast growth. Prostaglandin E2 and cysteinyl leukotrienes C4 were evaluated; a significant difference was only found in their ratio. Conclusion Bronchiolitis is associated with elevated nasal percentage of ILC2. This cellular population could be the key element in the differential immune response between BCH and RW which share some mechanisms such us monocyte activation, vascular damage, and fibroblast repair. Lipid mediators could play a role in the evolution of the disease later in life through innate lymphoid cells.