ENAGenomicsMultiomicsAvery August, Microbiology & Immunology, Cornell Universityhttps://www.ebi.ac.uk/ena/browser/view/PRJNA270640Mus musculusMast cells are indispensable for LPS-induced septic hypothermia, in which TNF-α plays an essential role to initiate sepsis. Tec family non-receptor tyrosine kinases ITK and BTK regulate mast cell-derived TNF-α in response to allergic antigen, but their role in LPS-induced TNF-α production by mast cells and related pathology is unclear. We sought to investigate the role(s) of ITK and BTK in mast cell response in septic condition. We found that the absence of ITK and BTK leads to enhanced TNF-α production by bone marrow-derived mast cells (BMMC). Itk-/-Btk-/- mast cells exhibit hyperactive preformed and LPS-induced TNF-α production, along with enhanced expression of other related genes such as NF-κB targeted genes, compared to WT cells. Overall design: Bone marrow cells from 8-week old WT, Itk-/-, Btk-/- and Itk-/-Btk-/- (double knockout: DKO) C57Bl/6 mice were cultured in murine Interleukin-3/Stem cell factor (IL-3/SCF) supplemented medium for 5 weeks to derive mast cells. WT, Itk-/-, Btk-/- and DKO bone marrow-derived mast cells (BMMC) were factor starved in medium without IL-3/SCF for 12 hours, followed by treatment with PBS (control) or 100 ng/ml LPS for 1 hour. Triplicates of each group were subjected to mouse whole genome genechip microarray analysis. Replicates were randomized on different chips to avoid systematic error.xref:PubMed:26581914xref:PubMed:27081634ENATcsk, fic, src-4, Thymocyte Stimulating Factor, para Tyrosine, DmelCG8049, Thymus-Dependent Lymphocytes, Il-2, Dm SRC2, T-Lymphocyte, PPS1, C-src2, C-src4, Interleukin II, T Lymphocyte, Roles, IL-2, Ro 23 6019, SRC 29A, DTec29, btk29A, Concepts, Mast, AT, lip pit syndrome, Kinase, RU-49637, immature T cell, Phosphotransferase, Interleukine 2, Dsrc28C, tissue basophil, aldesleukin, Ly87, response to endotoxin, tec29, T-Cells, Basophil, Lps, LPS, OFC6, 2-amino-3-(4-hydroxyphenyl)propanoic acid, 3-(p-Hydroxyphenyl)alanine, Tissue, PPS, Interleukin 2, T, LPFS1, Transphosphorylase, btk, Tissue Basophils, Y, Lymphocyte Mitogenic Factor, c-src/fps, LYK, T Cells, Dsrc29A, lipopolysaccharides, L Tyrosine, Tyr, mature T cell, Role Concepts, IL2, T-Cell Stimulating Factor, cleft lip and/or palate with mucous cysts of lower lip, Tyrosin, Tec29, ATP Phosphotransferases, ATK, T Lymphocytes, dsrc29A, PIT, Thymus Dependent Lymphocytes, RU 49637, Lymphocyte, ATP, Src29A, Mast Cell, 2-Amino-3-(p-hydroxyphenyl)propionic acid, xid, histaminocyte, DSrc28, VWS1, para-Tyrosine, Cell, Phosphotransferases, CG18355, mastocyte, T Cell Growth Factor, Concept, Tyrosine, Role Concept, Ro-23-6019, TCGF, T-Cell, tirosina, EMT, Tsk, Emt, Role, IMD1, VWS, S13, AGMX1, Basophils, CG8049, lymphokine, AI528679, T lymphocyte, BPK, Tec29A, CT41718, interleukin-2 receptor ligand, Transphosphorylases, T-cell, Aldesleukin, Ro 236019, Src2, Mitogenic Factor, Kinases, XLA, PSCTK2, PSCTK1, btk29a, RU49637, Thymus-Dependent, L-isomer, Ro-236019, T-Cell Growth Factor, Lymphocytes, Tissue Basophil, labrocyte, T-lymphocyte, Ran|M1, CT2415, Thymus-Dependent Lymphocyte, L isomer, Ran/M1, src4, T cell, src28C, T-cell growth factor, Ro236019, Cells, T Cell Stimulating Factor, Tec, T Cell, L-Tyrosine, Rasl2-8., src2Mus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisfalseMus musculusRole of IL-2 inducible T cell kinase (ITK) and Bruton's tyrosine kinase (BTK) in mast cell response to lipopolysaccharide (LPS)2025-09-242015-11-24PRJNA270640GSE64287100902708163426581914