The keratinocyte is the building block of the epidermis. Although it is structurally distinct with varying combinations of proteins, it performs numerous immunologic tasks that are continually being discovered. The body's first line of defense is often the skin. The immunologic microenvironment is dynamic and involves multiple arms of the immune system. Derrangements may lead to several disease states including cancer.
Pathogenesis Commonly Used Terms Internet Links
The keratinocyte is joined are a complex organization of proteins. The hemidesmosome are the glue between keratinocytes. It is composed of three components:
Inner plaque Connects with the keratin intermediate filaments of the cytoskeleton Outer plaque Extracellular sub-basal dense plate
Distinct proteins comprise the hemidesmosome and include:
Finally, the basal keratinocytes are joined to the basement membrane through a complex series of interactions.
Estimation of size of clonal unit for keratinocytes in normal human skin.
Chaturvedi V, Chu MD S, Carrol BS M, Brenner BS JW, Nickoloff BJ.
Department of Pathology, Loyola University Medical Center, Maywood, IL, USA.
Arch Pathol Lab Med 2002 Apr;126(4):420-4 Abstract quote
OBJECTIVE: It has been suggested that keratinocyte (KC) stem cells reside at the epicenter of a clonal population of cells. To estimate the territory or surface area covered by a single stem-cell-derived KC population in human skin, clonal skin maps were created from 3 healthy adult women and from normal skin of a psoriatic patient.
DESIGN: Two hundred fifty-eight punch biopsy samples of various sizes (ranging from 2 to 8 mm in diameter) were analyzed for clonality employing X chromosome inactivation patterns at the human androgen receptor gene (HUMARA) locus. DNA was isolated and clonality established by significant decrease of either maternal or paternal X chromosome band patterns following restriction enzyme digestion, polymerase chain reaction amplification, and gel electrophoresis.
RESULTS: Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35 five-mm biopsies revealed a clonal population of KCs. By contrast, in 5 different biopsies from a psoriatic patient, including 4- or 5-mm sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal population of KCs. Mantel-Haenszel chi(2) analysis revealed a P value of.001, reflecting a strong trend in probability for presence of a single clone of KCs as related to size of the biopsy sample. By sequentially analyzing 30 contiguous 2-mm biopsy samples within a given strip of skin, 10 clonal domain changes, as reflected in maternal versus paternal switches, were observed.
CONCLUSIONS: These results provide direct evidence of a clonal population of KCs in normal and psoriatic lesion-free skin, and indicate that a clonal epidermal unit of KCs frequently can be detected in small biopsies (2 mm), but that in normal skin sampling, overlapping clones are apparently present in larger (ie, 4-5-mm) biopsies, producing nonclonal patterns. The clonal domain of progeny in normal skin has a rather limited territorial boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic patient, there may be clonal expansion of KCs due to perturbation in epidermopoiesis and/or stem cell distribution.
Desmoglein as a target in autoimmunity and infection.
Department of Dermatology, Keio University School of Medicine.
J Am Acad Dermatol 2003 Feb;48(2):244-52 Abstract quote
Clinical phenotypes of most diseases are complex. However, once the mechanism behind the scene is clarified, the nature shows amazing beauty. There is a simple logic behind a complex disease. The exact molecular mechanism of the blister formation in staphylococcal scalded skin syndrome (SSSS) remained to be elucidated for 3 decades since exfoliative toxin was discovered by Melish and Glasgow in 1970.
A knowledge accumulated to understand the pathogenesis of pemphigus and cell-cell adhesion of keratinocytes led us to solve this question. Desmoglein 1, which is a cadherin type cell-cell adhesion molecule in desmosomes, is targeted in two different skin diseases, pemphigus foliaceus, and SSSS. In pemphigus foliaceus IgG autoantibodies are developed against desmoglein 1 and inhibit its adhesive function with resultant blister formation in the superficial epidermis.
In SSSS, exfoliative toxin produced by Staphylococcus aureus specifically binds and cleaves desmoglein 1 with resultant blister formation at the identical site.
p63 expression in normal human epidermis and epidermal appendages and their tumors.
Tsujita-Kyutoku M, Kiuchi K, Danbara N, Yuri T, Senzaki H, Tsubura A.
Departments of Pathology II and Plastic and Reconstructive Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
J Cutan Pathol 2003 Jan;30(1):11-7 Abstract quote
BACKGROUND: p63, a member of the p53 gene family, is expressed in basal cells of several different organs.
METHODS: The immunoreactivity of p63 was examined in normal human epidermis and epidermal appendages and their tumors, and compared with proliferative activity as evaluated by Ki-67.
RESULTS: In normal skin, p63 expression was seen in basal/suprabasal cells of the epidermis, outer root sheath and hair matrix cells of the hair follicle, seboblast situated in the outermost layer of sebaceous glands, and outer layer cells of the ductal portion and myoepithelial cells of the secretory portion of the sweat glands. p63 expression was confined to the cells forming a continuous basal rim along the normal epithelial structure. In tumors, p63 expression resembled that in normal tissue in that tumor components originating from p63-positive cells were constantly positive for p63. In normal and tumor tissues, not all p63-positive cells were positive for Ki-67.
CONCLUSIONS: p63 expression may be a marker of basal/progenitor cells in tumors of epidermis and epidermal appendages, and may be a diagnostic marker of these tumors.
Adv Dermatol 2000;16:113-157.
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Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
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DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 5th Edition. McGraw-Hill. 1999.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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