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Collagen and major histocompatibility class II expression in mesenchymal cells from CIITA hypomorphic mice.
Mol Immunol. 2007 Mar; 44(7):1709-21.MI

Abstract

Major histocompatibility class II (MHC II) transactivator (CIITA) is critical for interferon-gamma (IFN-gamma)-induced repression of collagen [Xu, Y., Wang, L., Buttice, G., Sengupta, P.K., Smith, B.D., 2004. Major histocompatibility class II transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by interferon gamma (IFN-gamma). J. Biol. Chem. 279, 41319-41332] and activation of MHC II transcription. To better understand the role of CIITA and IFN-gamma induced repression of collagen, mesenchymal cells (lung fibroblasts, adventitial fibroblasts, and smooth muscle cells) were isolated from a CIITA deficient mouse (C2ta(tm1Ccum)). IFN-gamma induced MHC II expression and repressed collagen type I expression in all three cell types isolated from the wild type background. As expected, IFN-gamma treatment of cells isolated from CIITA deficient mice did not induce MHC II production or activate the MHC II promoter. Interestingly, collagen gene expression and promoter activity was similar to that of wild type. Moreover, IFN-gamma induced CIITA mRNA and a truncated form of CIITA protein in all cells isolated from CIITA deficient mice. Most importantly, truncated CIITA occupied the collagen alpha 2(I) gene (col1a2) transcription start site during IFN-gamma treatment, but it did not occupy the MHC II promoter as judged by chromatin immunoprecipitation assays. Exogenous expression of a similar truncated form of CIITA maintained its ability to repress col1a2 transcription, but lost its ability to activate MHC II gene transcription suggesting a role for the CIITA C-terminal domain in activation, but not repression. IFN-gamma induced primarily types I and IV CIITA isoforms in the mouse cells. All three isoforms of CIITA were capable of repressing col1a2 and activating MHC II gene transcription. These data suggest that the previously described CIITA knockout mouse carries a hypomorphic mutation, rather than a null mutation. The removal of the leucine rich region in CIITA blocks activation of MHC II without altering repression of collagen transcription.

Authors+Show Affiliations

Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16982097

Citation

Xu, Yong, et al. "Collagen and Major Histocompatibility Class II Expression in Mesenchymal Cells From CIITA Hypomorphic Mice." Molecular Immunology, vol. 44, no. 7, 2007, pp. 1709-21.
Xu Y, McDonald J, Perloff E, et al. Collagen and major histocompatibility class II expression in mesenchymal cells from CIITA hypomorphic mice. Mol Immunol. 2007;44(7):1709-21.
Xu, Y., McDonald, J., Perloff, E., Butticè, G., Schreiber, B. M., & Smith, B. D. (2007). Collagen and major histocompatibility class II expression in mesenchymal cells from CIITA hypomorphic mice. Molecular Immunology, 44(7), 1709-21.
Xu Y, et al. Collagen and Major Histocompatibility Class II Expression in Mesenchymal Cells From CIITA Hypomorphic Mice. Mol Immunol. 2007;44(7):1709-21. PubMed PMID: 16982097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Collagen and major histocompatibility class II expression in mesenchymal cells from CIITA hypomorphic mice. AU - Xu,Yong, AU - McDonald,Jessica, AU - Perloff,Emily, AU - Butticè,Giovanna, AU - Schreiber,Barbara M, AU - Smith,Barbara D, Y1 - 2006/09/18/ PY - 2006/06/23/received PY - 2006/07/27/revised PY - 2006/07/28/accepted PY - 2006/9/20/pubmed PY - 2007/3/14/medline PY - 2006/9/20/entrez SP - 1709 EP - 21 JF - Molecular immunology JO - Mol Immunol VL - 44 IS - 7 N2 - Major histocompatibility class II (MHC II) transactivator (CIITA) is critical for interferon-gamma (IFN-gamma)-induced repression of collagen [Xu, Y., Wang, L., Buttice, G., Sengupta, P.K., Smith, B.D., 2004. Major histocompatibility class II transactivator (CIITA) mediates repression of collagen (COL1A2) transcription by interferon gamma (IFN-gamma). J. Biol. Chem. 279, 41319-41332] and activation of MHC II transcription. To better understand the role of CIITA and IFN-gamma induced repression of collagen, mesenchymal cells (lung fibroblasts, adventitial fibroblasts, and smooth muscle cells) were isolated from a CIITA deficient mouse (C2ta(tm1Ccum)). IFN-gamma induced MHC II expression and repressed collagen type I expression in all three cell types isolated from the wild type background. As expected, IFN-gamma treatment of cells isolated from CIITA deficient mice did not induce MHC II production or activate the MHC II promoter. Interestingly, collagen gene expression and promoter activity was similar to that of wild type. Moreover, IFN-gamma induced CIITA mRNA and a truncated form of CIITA protein in all cells isolated from CIITA deficient mice. Most importantly, truncated CIITA occupied the collagen alpha 2(I) gene (col1a2) transcription start site during IFN-gamma treatment, but it did not occupy the MHC II promoter as judged by chromatin immunoprecipitation assays. Exogenous expression of a similar truncated form of CIITA maintained its ability to repress col1a2 transcription, but lost its ability to activate MHC II gene transcription suggesting a role for the CIITA C-terminal domain in activation, but not repression. IFN-gamma induced primarily types I and IV CIITA isoforms in the mouse cells. All three isoforms of CIITA were capable of repressing col1a2 and activating MHC II gene transcription. These data suggest that the previously described CIITA knockout mouse carries a hypomorphic mutation, rather than a null mutation. The removal of the leucine rich region in CIITA blocks activation of MHC II without altering repression of collagen transcription. SN - 0161-5890 UR - https://www.unboundmedicine.com/medline/citation/16982097/Collagen_and_major_histocompatibility_class_II_expression_in_mesenchymal_cells_from_CIITA_hypomorphic_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0161-5890(06)00552-9 DB - PRIME DP - Unbound Medicine ER -