Differential expression of MHC class II antigens and cathepsin L by subtypes of cortical epithelial cells in the rat thymus: an immunoelectron microscopic study

Arudchelvan, Yamini; Nishimura, Yukio; Tokuda, Nobuko; Sawada, Teruo; Shinozaki, Fumihiko; Fukumoto, Tetsuo

doi:10.1093/jmicro/51.3.173

Cited by 9 publications

(4 citation statements)

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“…is at least remarkable. However, other studies have also shown that precursors of CTSL are found in the cytoplasm of epidermal keratinocytes (Kawada et al, 1997), and in the cytoplasm of cortical thymic epithelial cells (Arudchelvan et al, 2002). It has been coined that AEP, like CTSL, could be secreted from cells under some conditions, and may be active in the pericellular and intracellular environment (Barrett et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Colocalization of Cystatin M/E and Cathepsin V in Lamellar Granules and Corneodesmosomes Suggests a Functional Role in Epidermal Differentiation

Zeeuwen

Ishida‐Yamamoto

Vlijmen-Willems

et al. 2007

Journal of Investigative Dermatology

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Cystatin M/E is a cysteine protease inhibitor with two distinct binding sites for papain-like cysteine proteases (family C1) and the asparaginyl endopeptidase (AEP) legumain of family C13. We have previously demonstrated that deficiency of cystatin M/E in mice causes ichthyosiform skin changes and barrier disruption, which could be caused by unrestrained AEP activity. Recently, we provided biochemical evidence that human cathepsin V (CTSV) and cathepsin L (CTSL) are additional biological targets for human cystatin M/E. To address the possible role of these three proteases and their inhibitor in epidermal differentiation, we investigated the localization of these proteins in normal human skin. Whereas CTSL and AEP were broadly expressed in epithelial cells of the skin, we found a specific colocalization of cystatin M/E and CTSV in the stratum granulosum and in the root sheets of the hair follicle, using immunofluorescence microscopy. Immunoelectron microscopy revealed that cystatin M/E and CTSV are separately transported within the lamellar granules. Cystatin M/E was also found in the extracellular space in the stratum corneum associated with corneodesmosomes, where it was closely associated with CTSV. Based on the striking stratum-specific colocalization of cystatin M/E and CTSV, we propose that these molecules could have an important role in epidermal differentiation and desquamation.

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Section: Discussionmentioning

confidence: 99%

Colocalization of Cystatin M/E and Cathepsin V in Lamellar Granules and Corneodesmosomes Suggests a Functional Role in Epidermal Differentiation

Zeeuwen

Ishida‐Yamamoto

Vlijmen-Willems

et al. 2007

Journal of Investigative Dermatology

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“…It is of great consequence that processing is different between TECs and hemopoietically derived APCs. Importantly, TECs, but not APCs, have been shown to express cathepsin L (77–79), which may potentially influence the peptides presented for positive selection compared to negative selection. It has recently been shown that TCR‐transgenic thymocytes in competition for limited peptides can undergo further TCRα gene rearrangements to produce a receptor that may be selected more efficiently by other thymic self‐peptides (80).…”

Section: Thymocyte Selectionmentioning

confidence: 99%

Thymic generation and regeneration

Gill

Malin

Sutherland

et al. 2003

Immunological Reviews

130

102

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The thymus is a complex epithelial organ in which thymocyte development is dependent upon the sequential contribution of morphologically and phenotypically distinct stromal cell compartments. It is these microenvironments that provide the unique combination of cellular interactions, cytokines, and chemokines to induce thymocyte precursors to undergo a differentiation program that leads to the generation of functional T cells. Despite the indispensable role of thymic epithelium in the generation of T cells, the mediators of this process and the differentiation pathway undertaken by the primordial thymic epithelial cells are not well defined. There is a lack of lineage-specific cell-surface-associated markers, which are needed to characterize putative thymic epithelial stem cell populations. This review explores the role of thymic stromal cells in T-cell development and thymic organogenesis, as well as the molecular signals that contribute to the growth and expansion of primordial thymic epithelial cells. It highlights recent advances in these areas, which have allowed for a lineage relationship amongst thymic epithelial cell subsets to be proposed. While many fundamental questions remain to be addressed, collectively these works have broadened our understanding of how the thymic epithelium becomes specialized in the ability to support thymocyte differentiation. They should also facilitate the development of novel, rationally based therapeutic strategies for the regeneration and manipulation of thymic function in the treatment of many clinical conditions in which defective T cells have an important etiological role.

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“…MHC class II molecules are distributed largely on the plasma membrane, with a minority present within the cytoplasmic vacuoles. Additional data regarding the localization of MHC class II in cytoplasmic vacuoles of cTECs have been reported elsewhere (Farr and Sidman, 1984; Arudchelvan et al, 2002). The morphology of the MIICs described in the present study is consistent with that of the cytoplasmic vacuoles described by Nabarra and Andrianarison (1987a) and De Waal and Rademakers (1997).…”

Section: Discussionmentioning

confidence: 61%

Identification and characterization of major histocompatibility complex class II compartments in cortical thymic epithelial cells

et al. 2003

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Previous studies have concentrated on elucidating the subcellular localization of major histocompatibility (MHC) class II molecules mainly in B cells, macrophages, and dendritic cells. Despite very rich cell-surface expression of MHC class II molecules by cortical thymic epithelial cells (cTECs), little is known regarding the expression of these molecules by cTECs at the subcellular level. In the present study we focused on the identification and characterization of MHC class II compartments (MIICs) in cTECs in situ by immunogold electron microscopy (IEM). We found that MHC class II molecules were located exclusively in the cytoplasmic vacuoles, and we identified these MHC class II molecule-containing cytoplasmic vacuoles as MIICs in cTECs. These MIICs were immunopositive for early endosomal, late endosomal, and lysosomal markers. Moreover, in these MIICs, MHC class II molecules were colocalized with cathepsin L, H2-DM, class II-associated invariant chain (Ii), and class II-associated invariant chain peptide (CLIP). Similarly, Ii molecules were colocalized with endosomal and lysosomal markers, cathepsin L, and H2-DM in the vacuoles. Taken together, these results suggest that MIICs in cTECs represent conventional endocytic compartments. The colocalization of MHC class II molecule or Ii with cathepsin L and H2-DM in the MIICs suggests that MIICs in cTECs may be sites of Ii degradation and peptide loading. Anat Rec Part A 274A: 798 -806, 2003.

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Differential expression of MHC class II antigens and cathepsin L by subtypes of cortical epithelial cells in the rat thymus: an immunoelectron microscopic study

Cited by 9 publications

References 0 publications

Colocalization of Cystatin M/E and Cathepsin V in Lamellar Granules and Corneodesmosomes Suggests a Functional Role in Epidermal Differentiation

Colocalization of Cystatin M/E and Cathepsin V in Lamellar Granules and Corneodesmosomes Suggests a Functional Role in Epidermal Differentiation

Thymic generation and regeneration

Identification and characterization of major histocompatibility complex class II compartments in cortical thymic epithelial cells

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