Allergens and Irritants Transcriptionally Upregulate CD80 Gene Expression in Human Keratinocytes

Abstract

The human CD80 costimulatory molecule is an important signal between professional antigen-presenting cells and T helper cells. The immunobiology of CD80 expression by keratinocytes, especially during allergic and irritant contact dermatitis, however, is less well understood. CD80 cell surface expression and gene transcription by keratinocytes was increased when keratinocytes were exposed to certain allergens (chemicals that induce inflammation via hapten-specific T cells) and irritants (chemicals that are toxic to epidermal cells). Therefore, the human CD80 promoter was cloned and luciferase reporter constructs containing various promoter fragments were engineered. Promoter mapping of these CD80 constructs in transiently transfected keratinocytes showed that a construct containing the proximal 231 bp immediately upstream of the transcription start site of the CD80 promoter was most active in keratinocytes and was inducible to a level ranging from 2- to 10-fold higher in keratinocytes treated with certain allergens and irritants, compared with untreated keratinocytes. This pattern of promoter fragment activity in keratinocytes is identical to that found in professional antigen-presenting cells. This is the first demonstration that the CD80 promoter is active in keratinocytes and that this activity is further increased in keratinocytes treated with certain allergens and irritants. These data suggest that allergens and irritants may, in part, break peripheral tolerance by their direct effects on keratinocyte costimulatory molecule expression, thereby facilitating interactions with epidermotropic T helper cells via the CD80-CD28 or CTLA-4 pathways.

Human keratinocyte induction of rapid effector function in antigen‐specific memory CD4+ and CD8+ T cells

“…Expression of HLA class I was further up-regulated, raising the possibility that IFN-c may also promote increased presentation of antigen to CD8 + T cells. Previous studies have suggested that CD80 gene expression may be upregulated by allergen or inflammatory mediators [17,18]. However, we did not observe change in CD80 or CD86 expression following incubation with IFN-c staphylococcal enterotoxin B, LPS, corticosteroids, IL-2, IL-4, IL-5, IL-10 or IL-13 ( Fig.…”

Induction of B7-1 in podocytes is associated with nephrotic syndrome

“…In human keratinocytes, B7-1 gene expression is induced by allergens and irritants (16). In P815 mastocytoma tumor cells, B7-1 gene expression is induced by oxidative stress (17).…”

“…Little is known about B7-1 expression by non-bone marrow-derived cells. In human keratinocytes, B7-1 gene expression is upregulated by allergens and irritants (16). In P815 mastocytoma tumor cells, B7-1 gene expression is induced by oxidative stress (17), which is reminiscent of the induction of B7-1 in podocytes by puromycin, described below.…”

Viral Interference with B7-1 Costimulation: A New Role for Murine Cytomegalovirus Fc Receptor-1

“…For example, triggering of B7-1 blocks B cell proliferation and Ab production (55). Other examples include the induction of B7-1 in kidney podocytes, resulting in an increase in glomerular filtration and transient proteinuria (56) and the induction of B7-1 expression on keratinocytes by inflammatory stimuli (57). Therefore, the function of costimulatory molecules extends beyond their traditional role in T cell signaling and may explain the broader expression pattern of these molecules on cell types other than APC (reviewed in Ref.…”