2002 Bill Reed
International Travel Fellowship

Lutz Langbein, M.D., was awarded the Bill Reed International Travel Fellowship at the Society for Investigative Dermatology Meeting in Los Angeles in 2002.

Three new type II epithelial keratins, hK6irs2–4, are specifically expressed in different layers of the human hair follicle inner root sheath.

L. Langbein¹, M.A. Rogers², S. Praetzel1, H. Winter², and J. Schweizer²; German Cancer Research Center, ¹Dept. of Cell Biology and ²Tumor Cell Regulation, Heidelberg, Germany.

EMBO/Genebank analysis using the recently described human K6irs1 cDNA (Langbein, L. et al., J. Invest. Dermatol. 2002, in press) lead to the discovery of a BAC clone lying upstream of the hK6irs1 gene and harboring three novel type II keratin gene loci, one of which (termed hK6irs2 in this report), has been recently described at the cDNA level (Porter, R.M. et al, Br. J. Dermatol 145: 558-568, 2001). Analysis of a human scalp cDNA library lead to the isolation of full length cDNAs of the remaining two genes, which were termed hK6irs3 and hK6irs4. Specific antisera were produced for hK6irs2-4 by injection of specific peptides and used for Western blot analysis of hair follicle keratin extracts. The three keratins migrated at similar heights as the other K6 family members. Both in situ hybridization and immunohistochemistry on scalp and plucked beard hairs showed an exclusive expression of hK6irs1-4 in the inner root sheath (IRS) of the hair follicle, causative for their designation as K6irs. As previously described, hK6irs1 was found in all three layers of the IRS, namely Henle, Huxley and cuticle. hK6irs2 and 3 were sequentially expressed in the IRS cuticle, hK6irs3 starting just above the germinative cell pool and hK6irs2 initiating above the apex of the dermal papillae. mRNA detection of hK6irs2-4 ceased in the mid-follicular region, whereas the protein detection terminated precisely with the onset of abrupt terminal differentiation of the IRS cuticle. K6irs4 mRNA and protein was clearly restricted to the Huxley layer. Its synthesis began in the lower bulb region and could be detected in all living cells of the Huxley layer. hK6irs4 was also found in specialized Huxley cells, termed “Flügelzellen” (“winged cells”), which form foot processes passing through the Henle layer and abutting upon cells of the companion layer. These “Flügelzellen” are regularly scattered throughout the total length of the Henle layer, indicating that these cells are part of a larger tissue unit (i.e. companion layer, IRS), important for the optimal molding and the guidance of the growing hair shaft. In summary, we provide evidence that the IRS, similar to the interfollicular epidermis and the hair shaft, is built upon a series of specific, sequentially expressed epithelial keratins.