Development of Mouse Dendritic Cells from Lineage‐Negative c‐kit<sup>&lt;low</sup>Pluripotent Hemopoietic Stem Cells In Vitro

Feng, Biao; Inaba, Muneo; Lian, Zhe‐Xiong; Cui, Yunze; Toki, Junko; Ito, Tomoki; Jin, Tienan; Fan, Tianxue; Yang, Guoxiang; Chen, Yú; Kushida, Taketoshi; Ikehara, Susumu

doi:10.1634/stemcells.18-1-53

Cited by 14 publications

(11 citation statements)

References 38 publications

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“…Among these cytokines, only IL-3, but not FLT3-L, SCF, or IL-6, could expand HPs, a finding in agreement with those of previous reports [5], [6], over 10 days after floating cultivation in a low cell binding plate (Fig. 1a).…”

Section: Resultssupporting

confidence: 93%

Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells

et al. 2009

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BackgroundLimitations of the clinical efficacy of dendritic cell (DC)-based immunotherapy, as well as difficulties in their industrial production, are largely related to the limited number of autologous DCs from each patient. We here established a possible breakthrough, a simple and cytokine-based culture method to realize a log-scale order of functional murine DCs (>1,000-fold), which cells were used as a model before moving to human studies.Methodology/Principal FindingsFloating cultivation of lineage-negative hematopoietic progenitors from bone marrow in an optimized cytokine cocktail (FLT3-L, IL-3, IL-6, and SCF) led to a stable log-scale proliferation of these cells, and a subsequent differentiation study using IL-4/GM-CSF revealed that 3-weeks of expansion was optimal to produce CD11b+/CD11c+ DC-like cells. The expanded DCs had typical features of conventional myeloid DCs in vitro and in vivo, including identical efficacy as tumor vaccines.Conclusions/SignificanceThe concept of DC expansion should make a significant contribution to the progress of DC-based immunotherapy.

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Section: Resultssupporting

confidence: 93%

Cytokine-Based Log-Scale Expansion of Functional Murine Dendritic Cells

et al. 2009

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“…Investigations of c-kit function in dendritic cells have lagged because in-vitro development of bone-marrow-derived dendritic cells (BMDCs) from HSCs earmarked c-kit as being stem-cell-specific. These studies [27–29] reported decreased c-kit expression upon dendritic cell development and maturation in line with the general profile of c-kit loss upon HSC differentiation. In fact, tissue dendritic cells do show minimal expression of this receptor.…”

Section: C-kit Has Important Functions In Different Cell Types Includmentioning

confidence: 55%

Dendritic cell c-kit signaling and adaptive immunity

Oriss

Krishnamoorthy

Ray

et al. 2014

Current Opinion in Allergy &Amp; Clinical Immunology

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Purpose of review Binding of the receptor tyrosine kinase, c-kit, to its ligand, stem cell factor (SCF), mediates numerous biological functions. Important roles for c-kit in hematopoiesis, melanogenesis, erythropoiesis, spermatogenesis, and carcinogenesis are well documented. Similarly, activation of mast cells and eosinophils by c-kit ligation has long been known to result in degranulation with concomitant release of pro-inflammatory mediators including cytokines. This review will highlight a recently discovered function of c-kit in regulating the adaptive immune responses with relevance to allergic diseases. Recent findings Recent studies in a number of laboratories including our own highlight the previously unappreciated functions for c-kit in immunological processes. Increased expression of c-kit and its ligand, SCF, on dendritic cells by Th2/Th17-inducing stimuli leads to c-kit activation and immune skewing toward these subsets and away from Th1 responses. Treatment of dendritic cells with inhibitors of c-kit activation such as imatinib mesylate (Gleevec) induces breach of T-cell tolerance, skewing of responses toward Th1, and activation of natural killer cells. Summary Taken together, these observations suggest that the c-kit/SCF axis may be a useful target for redirecting deleterious immune responses in various disease settings, including allergic diseases that are often associated with Th2 and Th17 responses.

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“…Many studies have elucidated the role of cytokines required for the differentiation or maturation of DCs in vitro. [4][5][6][7] Although granulocyte-macrophage colony-stimulating factor (GM-CSF) is known to be essential for DC generation from BM progenitor cells, [8][9][10] the mediators responsible for subsequent differentiation and maturation of DCs are not fully understood. As for recruitment to the lymphoid tissues, recent studies proved that chemokines expressed in the lymphoid organs, including secondary lymphoid tissue chemokine (SLC, CCL21) and Epstein Barr virus-induced molecule 1 ligand chemokine (ELC, CCL19), play an important role in mobilization of mature DCs to the spleen and LN.…”

Section: Introductionmentioning

confidence: 99%