Phenotypic characterization of blood and lung ILC2 in asthmatics undergoing segmental allergen provocation

Aims and objective: To characterise the phenotype and function of human ILC2 in acute allergic lung inflammation. Methods: We isolated human ILC2 from blood and bronchoalveolar lavage (BAL) of asthmatic patients (n=7) before and 24h after a segmental allergen challenge with either grass or house dust mite allergen). Cells were characterized by surface marker expression, cytokine secretion and transcriptomics analysis. Mediators in BAL, serum and cell culture supernatants were measured by multiplex ELISA. Results: Segmental allergen challenge induced a Th2 inflammation characterised by BAL eosinophils increasing from 0.9±0.5% to 75±14.4% and accompanied by an increase in Th2 cytokines. While numbers of ILC2 in blood decreased upon allergen challenge (6.3 fold; p=0.047) a 25 fold increase was observed in the BAL from allergen challenged lung segments (p=0.016). BAL ILC2 showed lower expression of CCR4 than blood ILC2. The ligands for CCR4; CCL17 and CCL22 were increased in BAL after allergen provocation (p<0.05). BAL ILC2 revealed a distinct mRNA expression profile indicating up-regulation of the cytokine production, costimulatory and antigen presenting functions. ILC2 derived from BAL after challenge secreted spontaneously IL-5 and IL-13 in contrast to blood ILC2. Conclusion: During an acute allergic airway inflammation the blood ILC2 infiltrate the lung and acquire an activated phenotype with markers indicating a role in local T-cell activation. while blood ILC2 t do not change their phenotype in response to the inflammation in lung

Blood Brain Barrier and Neuroinflammation Are Critical Targets of IGF-1-Mediated Neuroprotection in Stroke for Middle-Aged Female Rats

Ischemia-induced cerebral infarction is more severe in older animals as compared to younger animals, and is associated with reduced availability of insulin-like growth factor (IGF)-1. This study determined the effect of post-stroke IGF-1 treatment, and used microRNA profiling to identify mechanisms underlying IGF-1’s neuroprotective actions. Post-stroke ICV administration of IGF-1 to middle-aged female rats reduced infarct volume by 39% when measured 24h later. MicroRNA analyses of ischemic tissue collected at the early post-stroke phase (4h) indicated that 8 out of 168 disease-related miRNA were significantly downregulated by IGF-1. KEGG pathway analysis implicated these miRNA in PI3K-Akt signaling, cell adhesion/ECM receptor pathways and T-and B-cell signaling. Specific components of these pathways were subsequently analyzed in vehicle and IGF-1 treated middle-aged females. Phospho-Akt was reduced by ischemia at 4h, but elevated by IGF-1 treatment at 24h. IGF-1 induced Akt activation was preceded by a reduction of blood brain barrier permeability at 4h post-stroke and global suppression of cytokines including IL-6, IL-10 and TNF-α. A subset of these cytokines including IL-6 was also suppressed by IGF-1 at 24h post-stroke. These data are the first to show that the temporal and mechanistic components of post-stroke IGF-1 treatment in older animals, and that cellular components of the blood brain barrier may serve as critical targets of IGF-1 in the aging brain

Plasticity of innate lymphoid cell subsets

Innate lymphoid cells (ILCs) are important for tissue homeostasis and for the initiation of immune responses. Based on their transcriptional regulation and cytokine profiles, ILCs can be categorized into five subsets with defined phenotypes and functional profiles, but they also have the ability to adapt to local environmental cues by changing these profiles. This plasticity raises the question of the extent to which the cytokine production profiles of ILCs are pre-programmed or are a reflection of the tissue microenvironment. Here, we review recent advances in research on ILCs, with a focus on the plasticity of these cells. We highlight the ability of ILCs to communicate with the surrounding microenvironment and discuss the possible consequences of ILC plasticity for our understanding of the biological roles of these cells. Finally, we discuss how we might use this knowledge of ILC plasticity to develop or improve options for the treatment of inflammatory diseases