Abstract
New Zealand Black (NZB) mice have been well documented to have a variety of thymic epithelial cell microenvironmental abnormalities, including disruption of corticoepithelial cell networks and medullary cell clusters. These abnormalities of the thymic stromal network are particularly important because similar observations have been noted in other models of murine lupus. Thymic epithelial cells, a key component of the microenvironment, play an important role in selection of the mature T cell receptor repertoire. Recently, a homotypic calcium-independent human and murine epithelial cell adhesion molecule, Ep-CAM, has been described which is located at the thymocyto-cortical cell junction. The function of Ep-CAM is still unclear but its unique location within the thymus suggests that it is critical in the process of providing maturation signals. Consequently, we examined the thymic expression of Ep-CAM in a series of autoimmune prone mice by thymic distribution of Ep-CAM in NZB, NZW, NZB/W, BXSB-Yaa, MRL-Ipr/Ipr, C3H-gld/gld and the control strains BALB/c, C57BL6, C3H and MRL(+/+) by immunohistology and flow cytometry. Interestingly, NZB mice are similar to control mice from day 4 to 2 weeks of age, having a very low expression of Ep-CAM at the thymocyto-cortical junction. In control strains, there is a marked increased in expression of Ep-CAM beginning at 5 weeks of age. In contrast, NZB mice fail to show significant expression of Ep-CAM even well into adulthood. This abnormality of NZB mice was also noted in NZB/W F1 and BXSB mice, but not MRL-lpr/lpr or C3H-gld/gld mice. Given the potential importance of Ep-CAM in thymic selection, this study provides important evidence that a defective stromal microenvironment is likely to be of etiological significance in the susceptibility of NZB to autoimmune disease.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 393-404 |
| Number of pages | 12 |
| Journal | Journal of Autoimmunity |
| Volume | 13 |
| Issue number | 4 |
| DOIs | |
| State | Published - Dec 1999 |
Fingerprint
Keywords
- Autoimmunity
- Ep-CAM
- Lupus
- Thymic microenvironment
- Thymus
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Abnormal thymic expression of epithelial cell adhesion molecule (Ep-CAM) in New Zealand Black (NZB) mice. / Taguchi, Nobuhisa; Hashimoto, Yoshiko; Naiki, Mitsuru; Farr, Andrew G.; Boyd, Richard L.; Ansari, Aftab A.; Shultz, Leonard D.; Kotzin, Brian L.; Dorshkind, Kenneth; Ikehara, Susumu; Gershwin, M. Eric.
In: Journal of Autoimmunity, Vol. 13, No. 4, 12.1999, p. 393-404.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Abnormal thymic expression of epithelial cell adhesion molecule (Ep-CAM) in New Zealand Black (NZB) mice
AU - Taguchi, Nobuhisa
AU - Hashimoto, Yoshiko
AU - Naiki, Mitsuru
AU - Farr, Andrew G.
AU - Boyd, Richard L.
AU - Ansari, Aftab A.
AU - Shultz, Leonard D.
AU - Kotzin, Brian L.
AU - Dorshkind, Kenneth
AU - Ikehara, Susumu
AU - Gershwin, M. Eric
PY - 1999/12
Y1 - 1999/12
N2 - New Zealand Black (NZB) mice have been well documented to have a variety of thymic epithelial cell microenvironmental abnormalities, including disruption of corticoepithelial cell networks and medullary cell clusters. These abnormalities of the thymic stromal network are particularly important because similar observations have been noted in other models of murine lupus. Thymic epithelial cells, a key component of the microenvironment, play an important role in selection of the mature T cell receptor repertoire. Recently, a homotypic calcium-independent human and murine epithelial cell adhesion molecule, Ep-CAM, has been described which is located at the thymocyto-cortical cell junction. The function of Ep-CAM is still unclear but its unique location within the thymus suggests that it is critical in the process of providing maturation signals. Consequently, we examined the thymic expression of Ep-CAM in a series of autoimmune prone mice by thymic distribution of Ep-CAM in NZB, NZW, NZB/W, BXSB-Yaa, MRL-Ipr/Ipr, C3H-gld/gld and the control strains BALB/c, C57BL6, C3H and MRL(+/+) by immunohistology and flow cytometry. Interestingly, NZB mice are similar to control mice from day 4 to 2 weeks of age, having a very low expression of Ep-CAM at the thymocyto-cortical junction. In control strains, there is a marked increased in expression of Ep-CAM beginning at 5 weeks of age. In contrast, NZB mice fail to show significant expression of Ep-CAM even well into adulthood. This abnormality of NZB mice was also noted in NZB/W F1 and BXSB mice, but not MRL-lpr/lpr or C3H-gld/gld mice. Given the potential importance of Ep-CAM in thymic selection, this study provides important evidence that a defective stromal microenvironment is likely to be of etiological significance in the susceptibility of NZB to autoimmune disease.
AB - New Zealand Black (NZB) mice have been well documented to have a variety of thymic epithelial cell microenvironmental abnormalities, including disruption of corticoepithelial cell networks and medullary cell clusters. These abnormalities of the thymic stromal network are particularly important because similar observations have been noted in other models of murine lupus. Thymic epithelial cells, a key component of the microenvironment, play an important role in selection of the mature T cell receptor repertoire. Recently, a homotypic calcium-independent human and murine epithelial cell adhesion molecule, Ep-CAM, has been described which is located at the thymocyto-cortical cell junction. The function of Ep-CAM is still unclear but its unique location within the thymus suggests that it is critical in the process of providing maturation signals. Consequently, we examined the thymic expression of Ep-CAM in a series of autoimmune prone mice by thymic distribution of Ep-CAM in NZB, NZW, NZB/W, BXSB-Yaa, MRL-Ipr/Ipr, C3H-gld/gld and the control strains BALB/c, C57BL6, C3H and MRL(+/+) by immunohistology and flow cytometry. Interestingly, NZB mice are similar to control mice from day 4 to 2 weeks of age, having a very low expression of Ep-CAM at the thymocyto-cortical junction. In control strains, there is a marked increased in expression of Ep-CAM beginning at 5 weeks of age. In contrast, NZB mice fail to show significant expression of Ep-CAM even well into adulthood. This abnormality of NZB mice was also noted in NZB/W F1 and BXSB mice, but not MRL-lpr/lpr or C3H-gld/gld mice. Given the potential importance of Ep-CAM in thymic selection, this study provides important evidence that a defective stromal microenvironment is likely to be of etiological significance in the susceptibility of NZB to autoimmune disease.
KW - Autoimmunity
KW - Ep-CAM
KW - Lupus
KW - Thymic microenvironment
KW - Thymus
UR - http://www.scopus.com/inward/record.url?scp=17544389622&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=17544389622&partnerID=8YFLogxK
U2 - 10.1006/jaut.1999.0332
DO - 10.1006/jaut.1999.0332
M3 - Article
VL - 13
SP - 393
EP - 404
JO - Journal of Autoimmunity
JF - Journal of Autoimmunity
SN - 0896-8411
IS - 4
ER -