RESUMO
Epithelial cells have an ability termed 'cell competition', which is an immune surveillance-like function that extrudes precancerous cells from the epithelial layer, leading to apoptosis and clearance. However, it remains unclear how epithelial cells recognize and extrude transformed cells. Here, we discovered that a PirB family protein, leukocyte immunoglobulin-like receptor B3 (LILRB3), which is expressed on non-transformed epithelial cells, recognizes major histocompatibility complex class I (MHC class I) that is highly expressed on transformed cells. MHC class I interaction with LILRB3 expressed on normal epithelial cells triggers an SHP2-ROCK2 pathway that generates a mechanical force to extrude transformed cells. Removal of transformed cells occurs independently of natural killer (NK) cell or CD8+ cytotoxic T cell-mediated activity. This is a new mechanism in that the immunological ligand-receptor system generates a mechanical force in non-immune epithelial cells to extrude precancerous cells in the same epithelial layer.
Assuntos
Antígenos CD/metabolismo , Apoptose , Competição entre as Células , Células Epiteliais/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Neoplasias Pulmonares/metabolismo , Lesões Pré-Cancerosas/metabolismo , Receptores Imunológicos/metabolismo , Animais , Antígenos CD/genética , Subunidade alfa 1 de Fator de Ligação ao Core/metabolismo , Cães , Células Epiteliais/imunologia , Células Epiteliais/patologia , Células HaCaT , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Células Madin Darby de Rim Canino , Mecanotransdução Celular , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Lesões Pré-Cancerosas/genética , Lesões Pré-Cancerosas/imunologia , Lesões Pré-Cancerosas/patologia , Proteína Tirosina Fosfatase não Receptora Tipo 11/metabolismo , Células RAW 264.7 , Receptores Imunológicos/genética , Estresse Mecânico , Quinases Associadas a rho/metabolismoRESUMO
This study assessed the influence of different types of flooring on infants' crawling motion patterns and performance. Each participating infant (range: 8.7-12.4 months) was encouraged to crawl on a tatami mat made of woven straw as well as other flooring types such as hardwood, carpet, and joint mat. Material tests were conducted to quantify the friction and shock absorption of the flooring. A three-dimensional motion capture system was used to measure spatiotemporal and kinematic variables during hands-and-knees crawling. An increased crawling rate was associated with a faster cadence of cyclic arm movements, but not with crawling stride length. Hardwood flooring had a significantly lower crawling rate and longer duration of hand-floor contact than tatami, while the crawling stride length and range of motion of joint movements were hardly affected by flooring type. The results of this study suggest a drawback of hardwood flooring in terms of infants' effective quadrupedal locomotion.
Assuntos
Pisos e Cobertura de Pisos , Mãos , Fenômenos Biomecânicos , Humanos , Lactente , Joelho , Locomoção , MovimentoRESUMO
The developing retinotectal system of the Xenopus laevis tadpole is a model of choice for studying visual experience-dependent circuit maturation in the intact animal. The neurotransmitter gamma-aminobutyric acid (GABA) has been shown to play a critical role in the formation of sensory circuits in this preparation, however a comprehensive neuroanatomical study of GABAergic cell distribution in the developing tadpole has not been conducted. We report a detailed description of the spatial expression of GABA immunoreactivity in the Xenopus laevis tadpole brain at two key developmental stages: stage 40/42 around the onset of retinotectal innervation and stage 47 when the retinotectal circuit supports visually-guided behavior. During this period, GABAergic neurons within specific brain structures appeared to redistribute from clusters of neuronal somata to a sparser, more uniform distribution. Furthermore, we found that GABA levels were regulated by recent sensory experience. Both ELISA measurements of GABA concentration and quantitative analysis of GABA immunoreactivity in tissue sections from the optic tectum show that GABA increased in response to a 4 hr period of enhanced visual stimulation in stage 47 tadpoles. These observations reveal a remarkable degree of adaptability of GABAergic neurons in the developing brain, consistent with their key contributions to circuit development and function.