Biology subjects

Kılıc, A.

Publications and source records attributed to Kılıc, A..

2 recordsLinked to original sources

bioRxiv2022

Vitamin D constrains inflammation by modulating the expression of key genes on Chr17q12-21.1

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (1). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D mediated immunoregulation. Here we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases (2-4). We demonstrate increased vitamin D receptor (VDR) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3 encoded protein Aiolos to suppress IL-2-signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders. One Sentence SummaryVitamin D regulates two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, that are associated with autoimmune and chronic inflammatory diseases.

systems biology↗

bioRxiv2020

Genomic signatures of the unjamming transition in compressed human bronchial epithelial cells

Epithelial tissue has the capacity to switch from a collective phase that is quiescent, solidlike and non-migratory to one that is dynamic, fluid-like and migratory. In certain physiological and pathophysiological contexts this phenotypic switch has been attributed not to the well-known epithelial-to-mesenchymal transition, EMT, but rather to the recently discovered unjamming transition, UJT. UJT has been characterized thus far mainly at functional and morphological levels whereas underlying genome-wide molecular events remain largely unexplored. Using primary human bronchial epithelial cells and one well-defined trigger of UJT -mechanical compression- here we combine temporal RNA-Seq data and Protein-Protein Interaction networks to provide the first genome-wide analysis of UJT. Our results show that compression induces a multiphasic transcriptional response characterized by an early activation of genes regulating the membrane and actomyosin structure, and a delayed activation of genes regulating the extracellular matrix and cellmatrix interactions. This biphasic response is mediated by a cascade of signaling processes that promotes actin polymerization through the recruitment of integrin-ECM adhesive complexes and promotes increased cellular motility through activation of AP-1 transcription factors via ERK and JNK pathways. These findings, taken together, show that the UJT program is not the result of any single signaling pathway but rather comprises a coordinated interplay of downstream pathways including development, fate selection, energy metabolism, cytoskeletal reorganization, and adhesive interaction with extracellular matrix.

genomics↗