| First Author | Fan L | Year | 2003 |
| Journal | Proc Natl Acad Sci U S A | Volume | 100 |
| Issue | 6 | Pages | 3386-91 |
| PubMed ID | 12629221 | Mgi Jnum | J:82725 |
| Mgi Id | MGI:2654960 | Doi | 10.1073/pnas.0437899100 |
| Citation | Fan L, et al. (2003) Antigen presentation by keratinocytes directs autoimmune skin disease. Proc Natl Acad Sci U S A 100(6):3386-91 |
| abstractText | The antigen-presenting cells that initiate and maintain MHC class II-associated organ-specific autoimmune diseases are poorly defined. We now describe a new T cell antigen receptor (TCR) transgenic (Tg) model of inflammatory skin disease in which keratinocytes activate and are the primary target of autoreactive CD4(+) T cells. We previously generated keratin 14 (K14)-A(beta)b mice expressing MHC class II only on thymic cortical epithelium. CD4(+) T cells from K14-A(beta)b mice fail to undergo negative selection and thus have significant autoreactivity. The TCR genes from an autoreactive K14-A(beta)b CD4 hybridoma were cloned to produce a TCR Tg mouse, 2-2-3. 2-2-3 TCR Tg cells are negatively selected in WT C57BL6 mice but not in 2-2-3K14-A(beta)b mice. Interestingly, a significant number of mice that express both the K14-A(beta)b transgene and the autoreactive 2-2-3 TCR spontaneously develop inflammatory skin disease with mononuclear infiltrates, induction of MHC class II expression on keratinocytes, and T helper 1 cytokines. Disease can be induced by skin inflammation but not solely by activation of T cells. Thus, cutaneous immunopathology can be directed through antigen presentation by tissue-resident keratinocytes to autoreactive TCR Tg CD4(+) cells. |
