Редактирование: IL13 (раздел)

==Publications==

{{medline-entry
|title=A three-dimensional dementia model reveals spontaneous cell cycle re-entry and a senescence-associated secretory phenotype.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/32184029
|abstract=A hexanucleotide repeat expansion on chromosome 9 open reading frame 72 (C9orf72) is associated with familial amyotrophic lateral sclerosis (ALS) and a subpopulation of patients with sporadic ALS and frontotemporal dementia. We used inducible pluripotent stem cells from neurotypic and C9orf72  (C9 ) ALS patients to derive neuronal progenitor cells. We demonstrated that C9  and neurotypic neuronal progenitor cells differentiate into neurons. The C9  neurons, however, spontaneously re-expressed cyclin D1 after 12 weeks, suggesting cell cycle re-engagement. Gene profiling revealed significant increases in senescence-associated genes in C9  neurons. Moreover, C9  neurons expressed high levels of mRNA for [[CXCL8]], a chemokine overexpressed by senescent cells, while media from C9  neurons contained significant levels of [[CXCL8]], [[CXCL1]], [[IL13]], IP10, [[CX3CL1]], and reactive oxygen species, which are components of the senescence-associated secretory phenotype. Thus, re-engagement of cell cycle-associated proteins and a senescence-associated secretory phenotype could be fundamental components of neuronal dysfunction in ALS and frontotemporal dementia.
|mesh-terms=* Amyotrophic Lateral Sclerosis
* C9orf72 Protein
* Cell Cycle
* Cells, Cultured
* Cellular Senescence
* DNA Repeat Expansion
* Frontotemporal Dementia
* Gene Expression
* Gene Expression Regulation, Developmental
* Humans
* Induced Pluripotent Stem Cells
* Interleukin-8
* RNA, Messenger
* Stem Cells
|keywords=* Amyotrophic lateral sclerosis
* Cell cycle re-entry
* Frontotemporal dementia
* Senescence
* Senescence-associated secretory phenotype
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166179
}}
{{medline-entry
|title=Age-specific changes in the molecular phenotype of patients with moderate-to-severe atopic dermatitis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30685456
|abstract=Atopic dermatitis (AD) shows differential clinical presentation in older compared with younger patients. Nevertheless, changes in the AD molecular profile with age are unknown. We sought to characterize age-related changes in the AD profile. We evaluated age-specific changes in lesional and nonlesional tissues and blood from patients with moderate-to-severe AD (n = 246) and age-matched control subjects (n = 71) using immunohistochemistry, quantitative real-time PCR, and Singulex in a cross-sectional study. Patients were analyzed by age group (18-40, 41-60, and ≥61 years). Although disease severity/SCORAD scores were similar across AD age groups (mean, approximately 60 years; P = .873), dendritic cell infiltrates (CD1b  and FcεRI , P < .05) decreased with age. T 2 measures (IL5, [[IL13]], [[CCL13]], [[CCL18]], and CCL26) significantly decreased with age in patients with AD, despite increasing with age in control subjects. Consistent with T 2 axis decreases, serum IgE levels and eosinophil counts negatively correlated with age in patients with AD (r = -0.24 and r = -0.23, respectively; P < .05). T 22-secreted [[IL22]] expression levels also decreased with age uniquely in patients with AD (P < .05). Expression of T 1-related (IFNG, IL12/23p40, [[STAT1]], and CXCL9; P < .05 for CXCL9) and T 17-related (IL17A and IL20; P < .05 for IL20) markers increased with age in both patients with AD and control subjects. Expression of terminal differentiation measures significantly increased in older patients with AD (loricrin [LOR] and filaggrin [FLG], P < .05), whereas expression of S100As (S100A8, P < .01) and hyperplasia markers (epidermal thickness, keratin 16, and Ki67; P < .05 for keratin 16) decreased. Serum trends in AD mimicked skin findings, with T 2 downregulation (CCL26; r = -0.32, P < .1) and T 1 upregulation (IFN-γ; r = 0.48, P < .01) with age. The adult AD profile varies with age. Although T 1/T 17 skewing increases in both patients with AD and control subjects, patients with AD show unique decreases in T 2/T 22 polarization and normalization of epithelial abnormalities. Thus age-specific treatment approaches might be beneficial for AD.
|mesh-terms=* Adolescent
* Adult
* Aged
* Aged, 80 and over
* Aging
* Cytokines
* Dermatitis, Atopic
* Female
* Gene Expression
* Humans
* Male
* Middle Aged
* Phenotype
* Severity of Illness Index
* Skin
* Young Adult
|keywords=* Atopic dermatitis
* T(H)1
* T(H)17
* T(H)2
* T(H)22
* aging
* biomarker
* filaggrin
* hyperplasia
* loricrin
* skin
|full-text-url=https://sci-hub.do/10.1016/j.jaci.2019.01.015
}}
{{medline-entry
|title=[[IL10]]-driven [[STAT3]] signalling in senescent macrophages promotes pathological eye angiogenesis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/26260587
|abstract=Macrophage dysfunction plays a pivotal role during neovascular proliferation in diseases of ageing including cancers, atherosclerosis and blinding eye disease. In the eye, choroidal neovascularization (CNV) causes blindness in patients with age-related macular degeneration (AMD). Here we report that increased [[IL10]], not [[IL4]] or [[IL13]], in senescent eyes activates [[STAT3]] signalling that induces the alternative activation of macrophages and vascular proliferation. Targeted inhibition of both [[IL10]] receptor-mediated signalling and [[STAT3]] activation in macrophages reverses the ageing phenotype. In addition, adoptive transfer of [[STAT3]]-deficient macrophages into eyes of old mice significantly reduces the amount of CNV. Systemic and CD163( ) eye macrophages obtained from AMD patients also demonstrate [[STAT3]] activation. Our studies demonstrate that impaired [[SOCS3]] feedback leads to permissive [[IL10]]/[[STAT3]] signalling that promotes alternative macrophage activation and pathological neovascularization. These findings have significant implications for our understanding of the pathobiology of age-associated diseases and may guide targeted immunotherapy. 
|mesh-terms=* Aged
* Aged, 80 and over
* Aging
* Animals
* Eye
* Female
* Humans
* Interleukin-10
* Macrophages
* Macular Degeneration
* Male
* Mice
* Mice, Inbred C57BL
* Middle Aged
* Neovascularization, Pathologic
* Porphyrins
* RAW 264.7 Cells
* Receptors, Interleukin-10
* STAT3 Transcription Factor
* Suppressor of Cytokine Signaling 3 Protein
* Suppressor of Cytokine Signaling Proteins

|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4918330
}}