Functional Caspase-1 Is Required for Langerhans Cell Migration and Optimal Contact Sensitization in Mice

Antonopoulos, Christos; Cumberbatch, Marie; Dearman, Rebecca J.; Daniel, Richard J.; Kimber, Ian; Groves, Richard

doi:10.4049/jimmunol.166.6.3672

Cited by 103 publications

(75 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Caspase-1 and IL-1b have been previously implicated in the sensitization phase. 91,92 Similarly, NALP3-deficient mice that receive cells from wild-type sensitized animals develop the T-cell dependent elicitor phase, suggesting that NALP3 is involved in the sensitization phase and may bridge the TNP-Cl stress signal with the activation of the adaptive immunity. A related agent 2,4-dinitrofluorobenzene that is able to induce contact hypersensitivity promotes the release of IL-1b via caspase-1 in a skin dendritic cell line suggesting that the inflammasome may directly detect such compounds.…”

Section: Nalp3 and Activation Of The Adaptive Immune Systemmentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

View full text Add to dashboard Cite

Fifteen years have passed since the cloning and characterization of the interleukin-1b-converting enzyme (ICE/caspase-1), the first identified member of a family of proteases currently known as caspases. Caspase-1 is the prototypical member of a subclass of caspases involved in cytokine maturation termed inflammatory caspases that also include caspase-4 caspase -5, caspase -11 and caspase -12. Efforts to elucidate the molecular mechanisms involved in the activation of these proteases have uncovered an important role for the NLR family members, NALPs, NAIP and IPAF. These proteins promote the assembly of multiprotein complexes termed inflammasomes, which are required for activation of inflammatory caspases. This article will review some evolutionary aspects, biochemical evidences and genetic studies, underlining the role of inflammasomes and inflammatory caspases in innate immunity against pathogens, autoinflammatory syndromes and in the biology of reproduction. Inflammatory CaspasesThe history of caspases began with the identification of an aspartate-specific protease activity involved in the conversion of the 31 kDa proIL-1b precursor to its active 17 kDa biologically active form, 1,2 and the identification of caspase-1 as the protease responsible for proIL-1b maturation. 3,4 The subsequent discovery of ced-3, that shares similarities with caspase-1 and which is involved in programmed cell death (PCD) in Caenorhabditis elegans, suggested that caspases might play fundamental roles in apoptosis. 5 As reviewed in the papers accompanying this issue of Cell Death and Differentiation, the role of apoptotic caspases in C. elegans and in vertebrates is crucial and deal with many facets of cell biology, development and diseases. In this review, we will focus on a subset of caspases present only in vertebrates and known as inflammatory caspases.Inflammatory caspases (also known as group I caspases) are encoded by three main genes in humans caspase-1, caspase-4 and caspase-5 and three main genes in mouse, caspase-1, caspase-11 and caspase-12. 6,7 In mammals, these caspases are characterized by the presence of a CARD domain at the N-terminus (Figure 1a). Human, chimp and mouse inflammatory caspases share significant similarity and are organized in a single locus (Figure 1c). Phylogenetic analysis of the conserved CARD domain suggests that the inflammatory caspases can be separated in evolutionaryrelated clusters (Figure 1b). The caspase-1 cluster contains caspase-1 and four other genes encoding decoy caspases: cop, inca1, inca2 and iceberg. These decoy caspase-1-like genes are absent in the mouse genome, suggesting that they have arisen recently by duplication of caspase-1. Although human and mouse caspase-1 are likely orthologues, sequence analysis suggests that human caspase-4 and caspase-5 have originated from a duplication of caspase-11. 7 However, the human caspase-12 gene, which in the chimp genome contains an SHG box important for it enzymatic activity, 8 evolved towards an enzymatically inactive form at some stage...

show abstract

Section: Nalp3 and Activation Of The Adaptive Immune Systemmentioning

confidence: 99%

Inflammatory caspases and inflammasomes: master switches of inflammation

2006

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that the greatest reduction in epidermal LCs occurs at 4 hours. 39,45 In this study, 4 hours after application of oxazolone there was an expected Figure 5A). In normal mice there was a significant decline in LC frequency in sensitized skin compared with vector-treated skin (from 836 Ϯ 107 LC/mm 2 to 535 Ϯ 71 LC/mm 2 ; P Ͻ .001; Student t test) ( Figure 5B).…”

Section: Diminished Migration Of Wasp-null Lcs After Contact Sensitizmentioning

confidence: 99%

“…The method of LC quantification followed has been described previously. 39 Briefly, ears were excised and split into dorsal and ventral halves using fine forceps. Dorsal halves were incubated in 0.02 M EDTA at 37°C for 90 minutes to allow separation of the epidermis and dermis.…”

Section: Oxazolone Sensitization and Immunohistochemical Staining Of mentioning

confidence: 99%

Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein

Noronha

2005

Blood

109

102

View full text Add to dashboard Cite

IntroductionDendritic cells (DCs) are highly motile bone marrow-derived antigen-presenting cells (APCs). They have specialized migratory and homing properties that allow them both to initiate primary immune responses and to induce tolerance. 1,2 In lymphoid organs they are present as interdigitating cells in the white pulp of the spleen and in the paracortex of lymph nodes (LNs) where they are able to capture incoming foreign antigen from blood or lymph, respectively. In nonlymphoid tissues DCs act as sentinels of injury and patrol for the presence of foreign antigens and pathogens. Upon capture they migrate to draining secondary lymphoid tissue during which time they mature and develop the capacity to stimulate antigen specific T cells.The migration and spatial localization of DCs are controlled by numerous extrinsic factors, including chemokine family members to which they are responsive through maturation and localizationdependent mechanisms. [3][4][5][6][7] The physical motility of cells and anchorage in specific tissues is, however, ultimately dependent on the regulated dynamics of the actin cytoskeleton, which determines the response of cells to chemokine gradients and enables purposeful movement through the sequential process of leading-edge protrusion, attachment, and tail retraction. 8 The molecular control of this highly coordinated activity is orchestrated by Rho family guanosine triphosphatases (GTPases), the best characterized of which are Cdc42, Rac1/2, and RhoA, and their downstream effectors. 9 In hematopoietic cells, a key effector for Cdc42 is the Wiskott-Aldrich syndrome protein (WASp). WASp is a 502-amino acid member of a conserved family of proteins that participate in the organization of actin polymerization primarily through activation of the actin-related protein (Arp2/Arp3) complex. [10][11][12] Interference in these signaling pathways results in multiple cytoskeletal defects in DCs, including the failure to form normal membrane projections and specialized structures known as podosomes, which form behind the leading edge of motile cells. [13][14][15][16] Podosomes concentrate ␤2 integrins around an actin core and, although their function has not been clearly identified, are responsible for tight adhesion of cells to intercellular adhesion molecule-1 (ICAM-1) and possibly junctional adhesion molecule-A (JAM-A). [17][18][19] Furthermore, they are highly dynamic with a turnover of minutes, providing a migrating cell with a mechanism for rapid attachment and detachment, and with localized anchorage points that could facilitate traverse of endothelial barriers in particular.Wiskott-Aldrich syndrome (WAS) is characterized by microthrombocytopenia, immunodeficiency, eczema, and autoimmunity. 12 The pathophysiology of WAS relates to defective polymerization of [20][21][22][23][24][25][26] However, defects of migration identified in myeloid and T cells in vitro, and stem cells in vivo, [27][28][29][30][31] all support the hypothesis that many of the immunologic consequences of WASp deficiency ar...

show abstract

“…Epidermal sheets and epidermal single-cell suspensions were obtained as previously described (19,20). Cord blood was obtained following informed consent.…”

Section: Cell Preparationmentioning

confidence: 99%

“…Epidermal sheets were obtained as previously described (19) and were labeled with rat anti-mouse IA-IE-PE Ab (BD Pharmingen) (1/ 100 dilution) to detect LC. Samples were visualized by epifluorescent microscopy and images of six randomly chosen microscopic fields were acquired.…”

Section: Lc Countsmentioning

confidence: 99%

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

Barbaroux

Beleut

Brisken

et al. 2008

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Langerhans cells (LC) are the dendritic APC population of the epidermis, where they reside for long periods and are self-replicating. The molecular signals underlying these characteristics are unknown. The TNF superfamily member receptor activator of NF-κB ligand (RANKL, TNFSF11) has been shown to sustain viability of blood dendritic cells in addition to its role in promoting proliferation and differentiation of several cell types, notably osteoclasts. In this study, we have studied expression of the RANKL system in skin and have defined a key role for this molecule in LC homeostasis. In vitro and in vivo, human KC expressed RANKL and epidermal LC expressed cell surface RANK. In vitro, RANKL sustained CD34+ progenitor-derived LC viability following 72-h cultures in cytokine-free medium (79.5 ± 1% vs 55.2 ± 5.7% live cells, respectively; n = 4; p < 0.05). In vivo, RANKL-deficient mice displayed a marked reduction in epidermal LC density (507.1 ± 77.2 vs 873.6 ± 41.6 LC per mm2; n = 9; p < 0.05) and their proliferation was impaired without a detectable effect on apoptosis. These data indicate a key role for the RANKL system in the regulation of LC survival within the skin and suggest a regulatory role for KC in the maintenance of epidermal LC homeostasis.

show abstract

Functional Caspase-1 Is Required for Langerhans Cell Migration and Optimal Contact Sensitization in Mice

Cited by 103 publications

References 30 publications

Inflammatory caspases and inflammasomes: master switches of inflammation

Inflammatory caspases and inflammasomes: master switches of inflammation

Impaired dendritic-cell homing in vivo in the absence of Wiskott-Aldrich syndrome protein

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

Contact Info

Product

Resources

About