Biochemical and Biophysical Research Communications
CXCR4 engagement promotes dendritic cell survival and maturation
Section snippets
Materials and methods
Animals and reagent. Eight weeks old female C57BL/6 (B6) mice were purchased from Japan SLC (Hamamatsu, Japan) and maintained on a 12-h light/dark cycle under specific pathogen-free conditions. All protocols were approved by the Institutional Animal Care and Use Committee of the University of Occupational and Environmental Health.
For CXCR4 antagonist treatment, 4F-Benzoyl-TN14003 was used as CXCR4 antagonist [8], [9]. No toxicity of CXCR4 antagonist was observed at 5 μM as reported previously
CXCR4 expression in BMDCs and LCs
Initially, we evaluated the expression levels of CXCR4 on BMDCs by flow cytometry. BM cells were incubated in the culture medium with GM-CSF for 5 days. Significant amounts of CXCR4 were detected in the CD11c+ BMDCs, but CD11c− fraction expressed CXCR4 to a much lesser degree (Fig. 1A). We then compared the expression level of LCs. Among epidermal cell suspensions, CXCR4 was expressed on MHC class II+ epidermal LCs but merely barely detected on MHC class II− KCs (Fig. 1B).
Reduction of BMDC and LC numbers by CXCR4 antagonist treatment
To address whether
Discussion
It is a well accepted concept that chemokines are involved in not only chemotaxis but also other cellular events, such as survival, adhesion, proliferation, and differentiation [3]. For example, the roles of CCR7 on DCs have been well characterized in terms of maturation and differentiation [3]. On the other hand, the roles of CXCR4 on DCs remained largely unknown. Here, we showed that the numbers of BMDCs and LCs were decreased by CXCR4 antagonist in vitro. It is considered that LCs are
Acknowledgments
We thank Ms. Junko Nagai for technical assistance. The authors have no conflicting financial interests. This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan, Takeda Research Foundation, Cosmetology Research Foundation, Ono Research Foundation, and Lydia O’Leary Memorial Foundation.
References (21)
- et al.
T140 analogs as CXCR4 antagonists identified as anti-metastatic agents in the treatment of breast cancer
FEBS Lett.
(2003) - et al.
Superantigenic staphylococcal exotoxins induce T-cell proliferation in the presence of Langerhans cells or class II-bearing keratinocytes and stimulate keratinocytes to produce T-cell-activating cytokines
J. Invest. Dermatol.
(1994) - et al.
Stromal-cell derived factor is expressed by dendritic cells and endothelium in human skin
Am. J. Pathol.
(1999) - et al.
Stromal-derived factor-1 promotes the growth, survival, and development of human bone marrow stromal stem cells
Blood
(2005) - et al.
Cellular niches controlling B lymphocyte behavior within bone marrow during development
Immunity
(2004) - et al.
Dendritic cells and the control of immunity
Nature
(1998) - et al.
Dendritic-cell trafficking to lymph nodes through lymphatic vessels
Nat. Rev. Immunol.
(2005) - et al.
The multiple personalities of the chemokine receptor CCR7 in dendritic cells
J. Immunol.
(2006) - et al.
Rapid and coordinated switch in chemokine receptor expression during dendritic cell maturation
Eur. J. Immunol.
(1998) - et al.
Cutting edge: secondary lymphoid-tissue chemokine (SLC) and CC chemokine receptor 7 (CCR7) participate in the emigration pathway of mature dendritic cells from the skin to regional lymph nodes
J. Immunol.
(1999)
Cited by (41)
Strategy and application of manipulating DCs chemotaxis in disease treatment and vaccine design
2023, Biomedicine and PharmacotherapyDelivery of stromal-derived factor-1α via biocompatible gold nanoparticles promotes dendritic cells viability and migration
2021, Colloids and Surfaces A: Physicochemical and Engineering AspectsCitation Excerpt :Indeed, study showed that triggering of CXCL12-CXCR4 signaling in DCs plays a crucial role in the initiation of immune response by enhancing DC migration [16]. Furthermore, research also demonstrated that CXCL12-CXCR4 engagement enhances DCs maturation and survival to initiate acquired immune response [18]. Collectively, these data implicated important roles of CXCL12/SDF-1α on DCs functional maturation.
Beyond Chemoattraction: Multifunctionality of Chemokine Receptors in Leukocytes
2017, Trends in ImmunologyNatural killer T cells are essential for the development of contact hypersensitivity in BALB/c mice
2014, Journal of Investigative DermatologyHomeward bound: How do skin dendritic cells find their way into the lymph system
2012, Journal of Investigative DermatologyChemokine-mediated migration of mesencephalic neural crest cells
2011, CytokineCitation Excerpt :Migration may also be facilitated by inhibitory cues lining the migratory route [59]. In addition to regulating directed cell migration, SDF-1/CXCR4 signaling is also known to play a major role in cell survival, proliferation and maturation [60,61]. Survival of dendritic cells [60], and hematopoietic stem and progenitor cells [60] has been shown to depend on SDF-1/CXCR4 signaling.