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Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice

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Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice. / Sevenich, Lisa; Hagemann, Sascha; Stoeckle, Christina; Tolosa, Eva; Peters, Christoph; Reinheckel, Thomas.

In: BIOCHIMIE, Vol. 92, No. 11, 01.11.2010, p. 1674-80.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Sevenich, L, Hagemann, S, Stoeckle, C, Tolosa, E, Peters, C & Reinheckel, T 2010, 'Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice', BIOCHIMIE, vol. 92, no. 11, pp. 1674-80. https://doi.org/10.1016/j.biochi.2010.03.014

APA

Sevenich, L., Hagemann, S., Stoeckle, C., Tolosa, E., Peters, C., & Reinheckel, T. (2010). Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice. BIOCHIMIE, 92(11), 1674-80. https://doi.org/10.1016/j.biochi.2010.03.014

Vancouver

Sevenich L, Hagemann S, Stoeckle C, Tolosa E, Peters C, Reinheckel T. Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice. BIOCHIMIE. 2010 Nov 1;92(11):1674-80. https://doi.org/10.1016/j.biochi.2010.03.014

Bibtex

@article{4f1256d8795e42b3b09ce21f76e4d303,
title = "Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice",
abstract = "A genetic deficiency of the cysteine protease cathepsin L (Ctsl) in mice results in impaired positive selection of conventional CD4+ T helper cells as a result of an incomplete processing of the MHC class II associated invariant chain or incomplete proteolytic generation of positively selecting peptide ligands. The human genome encodes, in contrast to the mouse genome, for two cathepsin L proteases, namely cathepsin L (CTSL) and cathepsin V (CTSV; alternatively cathepsin L2). In the human thymic cortex, CTSV is the predominately expressed protease as compared to CTSL or other cysteine cathepsins. In order to analyze the functions of CTSL and CTSV in the positive selection of CD4+ T cells we employed Ctsl knock-out mice crossed either with transgenic mice expressing CTSL under the control of its genuine human promoter or with transgenic mice expressing CTSV under the control of the keratin 14 (K14) promoter, which drives expression to the cortical epithelium. Both human proteases are expressed in the thymus of the transgenic mice, and independent expression of both CTSL and CTSV rescues the reduced frequency of CD4+ T cells in Ctsl-deficient mice. Moreover, the expression of the human cathepsins does not change the number of CD4+CD25+Foxp3+ regulatory T cells, but the normalization of the frequency of conventional CD4+ T cell in the transgenic mice results in a rebalancing of conventional T cells and regulatory T cells. We conclude that the functional differences of CTSL and CTSV in vivo are not mainly determined by their inherent biochemical properties, but rather by their tissue specific expression pattern.",
keywords = "Animals, Antigens, CD4, Cathepsin L, Cathepsins, Cysteine Endopeptidases, Forkhead Transcription Factors, Gene Expression, Gene Knockout Techniques, HLA-D Antigens, Haplotypes, Humans, Interleukin-2 Receptor alpha Subunit, Mice, T-Lymphocytes, Helper-Inducer, T-Lymphocytes, Regulatory, Thymus Gland, Transgenes",
author = "Lisa Sevenich and Sascha Hagemann and Christina Stoeckle and Eva Tolosa and Christoph Peters and Thomas Reinheckel",
note = "Copyright {\textcopyright} 2010 Elsevier Masson SAS. All rights reserved.",
year = "2010",
month = nov,
day = "1",
doi = "10.1016/j.biochi.2010.03.014",
language = "English",
volume = "92",
pages = "1674--80",
journal = "BIOCHIMIE",
issn = "0300-9084",
publisher = "Elsevier",
number = "11",

}

RIS

TY - JOUR

T1 - Expression of human cathepsin L or human cathepsin V in mouse thymus mediates positive selection of T helper cells in cathepsin L knock-out mice

AU - Sevenich, Lisa

AU - Hagemann, Sascha

AU - Stoeckle, Christina

AU - Tolosa, Eva

AU - Peters, Christoph

AU - Reinheckel, Thomas

N1 - Copyright © 2010 Elsevier Masson SAS. All rights reserved.

PY - 2010/11/1

Y1 - 2010/11/1

N2 - A genetic deficiency of the cysteine protease cathepsin L (Ctsl) in mice results in impaired positive selection of conventional CD4+ T helper cells as a result of an incomplete processing of the MHC class II associated invariant chain or incomplete proteolytic generation of positively selecting peptide ligands. The human genome encodes, in contrast to the mouse genome, for two cathepsin L proteases, namely cathepsin L (CTSL) and cathepsin V (CTSV; alternatively cathepsin L2). In the human thymic cortex, CTSV is the predominately expressed protease as compared to CTSL or other cysteine cathepsins. In order to analyze the functions of CTSL and CTSV in the positive selection of CD4+ T cells we employed Ctsl knock-out mice crossed either with transgenic mice expressing CTSL under the control of its genuine human promoter or with transgenic mice expressing CTSV under the control of the keratin 14 (K14) promoter, which drives expression to the cortical epithelium. Both human proteases are expressed in the thymus of the transgenic mice, and independent expression of both CTSL and CTSV rescues the reduced frequency of CD4+ T cells in Ctsl-deficient mice. Moreover, the expression of the human cathepsins does not change the number of CD4+CD25+Foxp3+ regulatory T cells, but the normalization of the frequency of conventional CD4+ T cell in the transgenic mice results in a rebalancing of conventional T cells and regulatory T cells. We conclude that the functional differences of CTSL and CTSV in vivo are not mainly determined by their inherent biochemical properties, but rather by their tissue specific expression pattern.

AB - A genetic deficiency of the cysteine protease cathepsin L (Ctsl) in mice results in impaired positive selection of conventional CD4+ T helper cells as a result of an incomplete processing of the MHC class II associated invariant chain or incomplete proteolytic generation of positively selecting peptide ligands. The human genome encodes, in contrast to the mouse genome, for two cathepsin L proteases, namely cathepsin L (CTSL) and cathepsin V (CTSV; alternatively cathepsin L2). In the human thymic cortex, CTSV is the predominately expressed protease as compared to CTSL or other cysteine cathepsins. In order to analyze the functions of CTSL and CTSV in the positive selection of CD4+ T cells we employed Ctsl knock-out mice crossed either with transgenic mice expressing CTSL under the control of its genuine human promoter or with transgenic mice expressing CTSV under the control of the keratin 14 (K14) promoter, which drives expression to the cortical epithelium. Both human proteases are expressed in the thymus of the transgenic mice, and independent expression of both CTSL and CTSV rescues the reduced frequency of CD4+ T cells in Ctsl-deficient mice. Moreover, the expression of the human cathepsins does not change the number of CD4+CD25+Foxp3+ regulatory T cells, but the normalization of the frequency of conventional CD4+ T cell in the transgenic mice results in a rebalancing of conventional T cells and regulatory T cells. We conclude that the functional differences of CTSL and CTSV in vivo are not mainly determined by their inherent biochemical properties, but rather by their tissue specific expression pattern.

KW - Animals

KW - Antigens, CD4

KW - Cathepsin L

KW - Cathepsins

KW - Cysteine Endopeptidases

KW - Forkhead Transcription Factors

KW - Gene Expression

KW - Gene Knockout Techniques

KW - HLA-D Antigens

KW - Haplotypes

KW - Humans

KW - Interleukin-2 Receptor alpha Subunit

KW - Mice

KW - T-Lymphocytes, Helper-Inducer

KW - T-Lymphocytes, Regulatory

KW - Thymus Gland

KW - Transgenes

U2 - 10.1016/j.biochi.2010.03.014

DO - 10.1016/j.biochi.2010.03.014

M3 - SCORING: Journal article

C2 - 20347002

VL - 92

SP - 1674

EP - 1680

JO - BIOCHIMIE

JF - BIOCHIMIE

SN - 0300-9084

IS - 11

ER -