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Transcriptional profilling of In vitro-primed C.rodentium-specific WT or Caspase-1 deficient Th cells

ABSTRACT: Introduction: We reported that caspase-1 is highly expressed in in vitro-primed C.rodentium-specific Th cells. Caspase-1 deficient (Casp1d10) naïve T cells differentiate into pathogen-specific Th17 cells at an suboptimal level and fail to protect against C.rodentium infection. To gain insight into the regulatory pathways exerted by caspase-1 in Th cells, we performed RNA-seq on in vitro-primed WT and Casp1d10 Th cells. Method: We stimulated WT C57/BL6J splenic CD11c+ DCs with 10ug/ml C.rodentium lysate for 5 hours. Then DCs are washed and co-cultured in 1:5 ratio with naïve WT C57/BL6J or Casp1d10 CD4 T cells for 10 days. CFSE-CD90+ (pathogen-specific Th cells) were FACS-sorted and subjected to mRNA-seq analysis. Conclusion: We found that WT Cr-specific Th cells have higher expression of Th17 genes, including Il17a,f,Il22 and Rorc. Casp1Δ10 Cr-specific Th cells exhibited higher expression of iNOS genes and exogenous lipid metabolism genes such as Cd36, suggesting a distinct cellular metabolism potentially regulated by Caspase-1.

ORGANISM(S): Mus musculus

PROVIDER: GSE141062 | GEO | 2020/01/10

REPOSITORIES: GEO

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Transcriptional profilling of pathogen-specific T helper cells

Project description:Introduction: We reported a in vitro pathogen-specific priming system to using pathogen lysate stimulated splenic CD11c+ DCs to differentiate pathogen-specific murine T helper cells. This method allowed us to compare side-by-side transcriptional profiles of bulk T helper cells that are specific to distinct pathogens and to study their composition and functionality. Method: We stimulated mouse splenic CD11c+ DCs with 10ug/ml Lm or Cr lysate for 5hours. The DCs were subsequently washed and co-cultured at 1:5 ratio to purified, CFSE-labeled CD62L+CD44- mouse naïve CD4 T cells. At day-7, CD90+CFSE- (Pathogen-specific Th cells) or CD90+CFSE+ (naive T cells) were sorted from the same culture and were subjected to RNA isolation, library prep and subsequent sequencing. Conclusion: We found that Lm- and Cr-specific Th cells have distinct transcriptomes and contained distinct Th subtypes. Lm-specific Th cells contained higher expressions of Th1-associated cytokines, while Cr-specific Th cells contained higher levels of Th17 associate cytokines and transcription factors. In addition, we have identified heterogeneity within the pathogen-specific Th cells, as they express various cytokines from multiple Th lineages. Lastly, we found a vast variety of genes differentially expressed between Lm- and Cr-specific Th cells, indicating that different pathogen-stimulated DCs denote distinct function and developmental cues to T cells during differentiation.

2020-01-10 | GSE141054 | GEO

Transcriptional profilling of In vitro-primed C.rodentium-specific Th17 cells, cytokine-differentiated Th17 cells and ex vivo Th17 cells following C.rodentium infection

Project description:Introduction: We reported a in vitro pathogen-specific priming system to using pathogen lysate stimulated splenic CD11c+ DCs to differentiate pathogen-specific murine T helper cells. This method allowed us to compare side-by-side transcriptional profiles of bulk T helper cells that are specific to distinct pathogens and to study their composition and functionality. Moreover, we can utilize cytokine reporter mice to isolate specific Th subtypes from these in vitro-primed T cells and study their transcriptional regulation. Method: We isolate commited Th17 cells by utilizing IL-17A fate-mapping mice (Il17aCRE; R26tdT). We generated Th17 cells in 3 conditions: 1. We used Cr-stimulated DCs to prime Th17 cells and sorted CD90+CFSE-tdT+ population, dubbed 'ppTh17' cells. CFSE+CD90+ naive T cells from the same culture as controls. 2. We polarized naive Il17aCRE; R26tdT CD4 T cells to Th17 lineage using previously defined cytokine and antibody cocktail (IL-6+TGFb1+IL-1b+IL-23; plate bound anti-CD3+anti-CD28). We sorted CD90+tdT+ population, dubbed 'cdTh17' cells. 3. We intragastrically infected Il17aCRE; R26tdT mice with 5x10^8 C.rodentium and harvested mesenteric lymph nodes at 10 days post infection (dpi). We sorted tdT+ CD4 T cells from mesenteric lymph nodes, dubbed "ex vivo Th17' cells. The four sorted populations were subjected to mRNA-sequencing analysis. Conclusion: We found that compared to cdTh17 cells, ppTh17 cells and ex vivo Th17 cells resemble each other. These two physiologically relevant Th17 populations maintain high levels of heterogeneity and plasticity, as well as posess ability to upregulate memory T cell related genes. cdTh17 cells highly express glycolysis and one-carbon metabolism genes, correlate with their expression of cell cycle genes, suggesting a highly activated state.

2020-01-10 | GSE141061 | GEO

Transcriptional profilling of In vitro-primed C.rodentium-specific WT or Caspase-1 deficient Th cells

Project description:Transcriptional profilling of In vitro-primed C.rodentium-specific WT or Caspase-1 deficient Th cells

| PRJNA591907 | ENA

Essential role for CD30-Transglutaminase 2 axis in memory Th1 and Th17 cell generation.

Project description:Memory helper T (Th) cells are crucial for secondary immune responses against infectious microorganisms but also drive the pathogenesis of chronic inflammatory diseases. Therefore, it is of fundamental importance to understand how memory T cells are generated. However, the molecular mechanisms governing memory Th cell generation remain incompletely understood. Here, we identified CD30 as a molecule heterogeneously expressed on effector Th1 and Th17 cells, and CD30hi effector Th1 and Th17 cells preferentially generated memory Th1 and Th17 cells. We found that CD30 mediated signal induced Transglutaminase-2 (TG2) expression, and that the TG2 expression in effector Th cells is essential for memory Th cell generation. In fact, Cd30-deficiency resulted in the impaired generation of memory Th1 and Th17 cells, which can be rescued by overexpression of TG2. Furthermore, transglutaminase-2 (Tgm2)-deficient CD4 T cells failed to become memory Th cells. As a result, T cells from Tgm2-deficient mice displayed impaired antigen-specific antibody production and attenuated Th17-mediated allergic responses. Our data indicate that CD30-induced TG2 expression in effector Th cells is essential for the generation of memory Th1 and Th17 cells, and that CD30 can be a marker for precursors of memory Th1 and Th17 cells.

2020-06-04 | GSE151691 | GEO

Essential role for CD30-Transglutaminase 2 axis in memory Th1 and Th17 cell generation.

2020-05-28 | GSE151301 | GEO

Project description:Fecal gut flora of C57/BL6J mice

| PRJNA854286 | ENA

Cytokine profile of mature WT bone marrow-derived dendritic cells and fascin1 knockout bone marrow-derived dendritic cells

Project description:Cytokines secreted by WT and fascin1 KO BM-DCs maturated by LPS were determined by RayBio Quantibody mouse Th17 array1. Fascin1 KO BM-DCs show reduced secretion of several cytokines including IL-6.

2021-05-12 | GSE174285 | GEO

The kinases MEKK2 and MEKK3 regulate Transforming Growth Factor-β-mediated helper T cell differentiation

Project description:Mitogen-activated protein kinases (MAPKs) are key mediators of the T cell receptor (TCR) signals but their roles in T helper (Th) cell differentiation are unclear. Here we showed that the MAPK kinase kinases MEKK2 (encoded by Map3k2) and MEKK3 (encoded by Map3k3),negatively regulated transforming growth factor-beta (TGF-beta)-mediated Th cell differentiation.Map3k2-/-Map3k3Lck-Cre/- mice showed an abnormal accumulation of regulatory T (Treg) and Th17 cells in the periphery, consistent with Map3k2-/-Map3k3Lck-Cre/- naïve CD4+ T cells’ differentiation into Treg and Th17 cells with a higher frequency than wild-type (WT) cells after TGF-beta stimulation in vitro. In addition, Map3k2-/-Map3k3Lck-Cre/- mice developed more severe experimental autoimmune encephalomyelitis. Map3k2-/-Map3k3Lck-Cre/- T cells exhibited impaired phosphorylation of the SMAD2 and SMAD3 proteins at their linker regions, which negatively regulated the TGF-beta responses in T cells. Thus, the crosstalk between TCR-induced MAPK and the TGF-beta signaling pathways is important in regulating Th cell differentiation. CD4+CD62L-CD44+ cells were FACS sorted from C57BL/6 Lck-Cre MEKK2 KO MEKK3F/-(dKO) or C57BL/6 WT mice

2011-02-02 | E-GEOD-26987 | biostudies-arrayexpress

Markers of persistent multifunctional memory CD4+ T cells in latent TB infection

Project description:In latent tuberculosis infection (LTBI) spread of the bacteria is contained by a persistent immune response, which includes CD4+ T cells as important contributors. Here we show that TB-specific CD4+ T cells have a characteristic chemokine expression signature (CXCR3+CCR6+CCR4-; Th* cells), and that the overall number of Th* cells is significantly increased in LTBI donors. We have comprehensively characterized the transcriptional signature of Th* cells and find significant differences to conventional Th1, Th17 and Th2 cells, but no major changes between healthy and LTBI donors. Th* cells display linage-specific signatures of both Th1 and Th17 cells, but also have a unique gene expression program including genes associated with susceptibility to TB, enhanced T cell activation, enhanced cell survival, and induction of a cytotoxic program akin to CTL cells. Overall, the gene expression signature of Th* reveals characteristics of cells important in controlling latent infections.

2014-07-18 | GSE56179 | GEO

Mus musculus strain:C57/BL6j

Project description:Mus musculus strain:C57/BL6j Raw sequence reads

| PRJNA688802 | ENA