Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Barbaroux, Jean-Baptiste; Beleut, Manfred; Brisken, Cathrin; Mueller, Christopher G.; Groves, Richard

doi:10.4049/jimmunol.181.2.1103

Cited by 39 publications

(40 citation statements)

References 40 publications

(48 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Using transgenic mice that overexpress CD40L or RANKL in keratinocytes, it has been shown that RANKL suppressed autoimmunity induced by CD40L (42). Interestingly, in this system the numbers of epidermal LCs were greatly reduced by CD40L (43), suggesting that CD40L might regulate LC numbers, as was recently suggested also for RANKL (44). Oral DCs have the capability to express RANK (Fig.…”

Section: Discussionsupporting

confidence: 59%

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Arizon

Nudel

Segev

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Excessive bone resorption is frequently associated with chronic infections and inflammatory diseases. Whereas T cells were demonstrated to facilitate osteoclastogenesis in such diseases, the role of dendritic cells, the most potent activators of naive T cells, remains unclear. Using a model involving inflammation-driven alveolar bone loss attributable to infection, we showed that in vivo ablation of Langerhans cells (LCs) resulted in enhanced bone loss. An increased infiltration of B and T lymphocytes into the tissue surrounding the bone was observed in LC-ablated mice, including receptor activator of NF-κB ligand (RANKL)-expressing CD4 + T cells with known capabilities of altering bone homeostasis. In addition, the absence of LCs significantly reduced the numbers of CD4 + Foxp3 + T-regulatory cells in the tissue. Further investigation revealed that LCs were not directly involved in presenting antigens to T cells. Nevertheless, despite their low numbers in the tissue, the absence of LCs resulted in an elevated activation of CD4 + but not CD8 + T cells. This activation involved elevated production of IFN-γ but not IL-17 or IL-10 cytokines. Our data, thus, reveal a protective immunoregulatory role for LCs in inflammation-induced alveolar bone resorption, by inhibiting IFN-γ secretion and excessive activation of RANKL + CD4 + T cells with a capability of promoting osteoclastogenesis.

show abstract

Section: Discussionsupporting

confidence: 59%

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Arizon

Nudel

Segev

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Also survival of terminally differentiated mo-DCs and CD34-mDCs required NF-kB activity, though the cells could be rescued from inhibitor-induced apoptosis by the simultaneous presence of activation signals. Reduced survival due to decreased NF-kB activity has been described even in the presence of activation stimuli (23,30,46,47), but these discrepancies probably result from differences in species, DC type, or experimental setup. Together, our data clearly show that canonical NF-kB plays a nonredundant role in the regulation of survival of differentiating as well as fully differentiated monocyte-and CD34-derived human myeloid DC.…”

Section: Discussionmentioning

confidence: 99%

A Nonredundant Role for Canonical NF-κB in Human Myeloid Dendritic Cell Development and Function

Laar

Bosch

Kooij

et al. 2010

The Journal of Immunology

View full text Add to dashboard Cite

The plastic role of dendritic cells (DCs) in the regulation of immune responses has made them interesting targets for immunotherapy, but also for pathogens or tumors to evade immunity. Functional alterations of DCs are often ascribed to manipulation of canonical NF-κB activity. However, though this pathway has been linked to murine myeloid DC biology, a detailed analysis of its importance in human myeloid DC differentiation, survival, maturation, and function is lacking. The myeloid DC subsets include interstitial DCs and Langerhans cells. In this study, we investigated the role of canonical NF-κB in human myeloid DCs generated from monocytes (monocyte-derived DCs [mo-DCs]) or CD34+ progenitors (CD34-derived myeloid DCs [CD34-mDCs]). Inhibition of NF-κB activation during and after mo-DC, CD34-interstitial DC, or CD34-Langerhans cell differentiation resulted in apoptosis induction associated with caspase 3 activation and loss of mitochondrial transmembrane potential. Besides regulating survival, canonical NF-κB activity was required for the acquisition of a DC phenotype. Despite phenotypic differences, however, Ag uptake, costimulatory molecule and CCR7 expression, as well as T cell stimulatory capacity of cells generated under NF-κB inhibition were comparable to control DCs, indicating that canonical NF-κB activity during differentiation is redundant for the development of functional APCs. However, both mo-DC and CD34-mDC functionality were reduced by NF-κB inhibition during activation. In conclusion, canonical NF-κB activity is essential for the development and function of mo-DCs as well as CD34-mDCs. Insight into the role of this pathway may help in understanding how pathogens and tumors escape immunity and aid in developing novel treatment strategies aiming to interfere with human immune responses.

show abstract

“…RANKL has already been found to play an important role in the regulation of numerous dendritic cell (DC) functions, such as enhancement of T-cell activation capacity (1), increased release of proinflammatory cytokines (2) and prolonged cell survival (3,4). Furthermore, RANKL is expressed on inflamed or activated keratinocytes and induces activation of epidermal Langerhans cells (LC) (5). Particularly, RANKL seems to induce LC to regulate peripheral numbers of CD4 + CD25 + regulatory T cells (T reg ) (6).…”

Section: Introductionmentioning

confidence: 99%

Tissue microarray analysis of RANKL in cutaneous lupus erythematosus and psoriasis

Toberer

Sykora

Göttel

et al. 2011

Experimental Dermatology

View full text Add to dashboard Cite

Recently, it was discovered that the receptor activator of nuclear factor jB (RANK) ⁄ RANK ligand (RANKL) is part of an important signal transduction pathway for tissue homoeostasis. Therefore, we were interested in investigating RANKL expression in the epidermis of skin lesions from patients with different subtypes of cutaneous lupus erythematosus (CLE) and psoriasis as well as normal healthy donors. Using the tissue microarray technique, skin biopsy specimens were evaluated by immunohistochemistry. RANKL showed a significantly increased expression in the epidermis of skin biopsy specimens from patients with psoriasis (median: 4, range: 0-5) compared to patients with CLE (median: 0, range: 0-4) (P < 0.001). No significant differences in epidermal RANKL expression between the CLE subtypes were detected. These data show a different expression of RANKL in the epidermis of skin lesions from patients with CLE compared to those with psoriasis suggesting that RANKL might play an important role in the pathogenesis of the disease.

show abstract

Epidermal Receptor Activator of NF-κB Ligand Controls Langerhans Cells Numbers and Proliferation

Cited by 39 publications

References 40 publications

Langerhans cells down-regulate inflammation-driven alveolar bone loss

Langerhans cells down-regulate inflammation-driven alveolar bone loss

A Nonredundant Role for Canonical NF-κB in Human Myeloid Dendritic Cell Development and Function

Tissue microarray analysis of RANKL in cutaneous lupus erythematosus and psoriasis

Contact Info

Product

Resources

About