Dendritic cells fused with human cancer cells: morphology, antigen expression, and T cell stimulation

Abstract Dendritic cells (DCs) are essential for the initiation of acquired immune responses through antigen acquisition, migration, maturation, and T-cell stimulation. One of the critical mechanisms in this response is the process actin nucleation and polymerization, which is mediated by several groups of proteins, including mammalian Diaphanous-related formins (mDia). However, the role of mDia in DCs remains unknown. Herein, we examined the role of mDia1 (one of the isoforms of mDia) in DCs. Although the proliferation and maturation of bone marrow-derived DCs were comparable between control C57BL/6 and mDia1-deficient (mDia1−/−) mice, adhesion and spreading to cellular matrix were impaired in mDia1−/− bone marrow–derived DCs. In addition, fluorescein isothiocyanate-induced cutaneous DC migration to draining lymph nodes in vivo and invasive migration and directional migration to CCL21 in vitro were suppressed in mDia1−/− DCs. Moreover, sustained T-cell interaction and T-cell stimulation in lymph nodes were impaired by mDia1 deficiency. Consistent with this, the DC-dependent delayed hypersensitivity response was attenuated by mDia1-deficient DCs. These results suggest that actin polymerization, which is mediated by mDia1, is essential for several aspects of DC-initiated acquired immune responses.

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Dendritic cells are susceptible to infection with wild-type adenovirus, inducing a differentiation arrest in precursor cells and inducing a strong T-cell stimulation

Journal of General Virology ◽

10.1099/vir.0.013920-0 ◽

2009 ◽

Vol 91 (5) ◽

pp. 1150-1154 ◽

Cited By ~ 7

Author(s):

T. Kessler ◽

K. Hamprecht ◽

T. Feuchtinger ◽

G. Jahn

Keyword(s):

Dendritic Cells ◽

T Cell ◽

Precursor Cells ◽

Wild Type ◽

Cell Stimulation ◽

T Cell Stimulation

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Wnt Effector TCF4 Is Dispensable for Wnt Signaling in Human Cancer Cells

Genes ◽

10.3390/genes9090439 ◽

2018 ◽

Vol 9 (9) ◽

pp. 439 ◽

Cited By ~ 12

Author(s):

Dusan Hrckulak ◽

Lucie Janeckova ◽

Lucie Lanikova ◽

Vitezslav Kriz ◽

Monika Horazna ◽

...

Keyword(s):

T Cell ◽

Wnt Signaling ◽

Cancer Cells ◽

Human Cancer ◽

Wnt Signaling Pathway ◽

Human Cells ◽

Cellular Systems ◽

Mouse Tissue ◽

T Cell Factor ◽

Human Cancer Cells

T-cell factor 4 (TCF4), together with β-catenin coactivator, functions as the major transcriptional mediator of the canonical wingless/integrated (Wnt) signaling pathway in the intestinal epithelium. The pathway activity is essential for both intestinal homeostasis and tumorigenesis. To date, several mouse models and cellular systems have been used to analyze TCF4 function. However, some findings were conflicting, especially those that were related to the defects observed in the mouse gastrointestinal tract after Tcf4 gene deletion, or to a potential tumor suppressive role of the gene in intestinal cancer cells or tumors. Here, we present the results obtained using a newly generated conditional Tcf4 allele that allows inactivation of all potential Tcf4 isoforms in the mouse tissue or small intestinal and colon organoids. We also employed the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 system to disrupt the TCF4 gene in human cells. We showed that in adult mice, epithelial expression of Tcf4 is indispensable for cell proliferation and tumor initiation. However, in human cells, the TCF4 role is redundant with the related T-cell factor 1 (TCF1) and lymphoid enhancer-binding factor 1 (LEF1) transcription factors.

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