Mechanism of Dinitrochlorobenzene-Induced Dermatitis in Mice: Role of Specific Antibodies in Pathogenesis

Abstract

BackgroundDinitrochlorobenzene-induced contact hypersensitivity is widely considered as a cell-mediated rather than antibody-mediated immune response. At present, very little is known about the role of antigen-specific antibodies and B cells in the development of dinitrochlorobenzene-induced hypersensitivity reactions, and this is the subject of the present investigation.Methodology/Principal FindingsData obtained from multiple lines of experiments unequivocally showed that the formation of dinitrochlorobenzene-specific Abs played an important role in the development of dinitrochlorobenzene-induced contact hypersensitivity. The appearance of dinitrochlorobenzene-induced skin dermatitis matched in timing the appearance of the circulating dinitrochlorobenzene-specific antibodies. Adoptive transfer of sera containing dinitrochlorobenzene-specific antibodies from dinitrochlorobenzene-treated mice elicited a much stronger hypersensitivity reaction than the adoptive transfer of lymphocytes from the same donors. Moreover, dinitrochlorobenzene-induced contact hypersensitivity was strongly suppressed in B cell-deficient mice with no DNCB-specific antibodies. It was also observed that treatment of animals with dinitrochlorobenzene polarized Th cells into Th2 differentiation by increasing the production of Th2 cytokines while decreasing the production of Th1 cytokines.Conclusions/SignificanceIn striking contrast to the long-held belief that dinitrochlorobenzene-induced contact hypersensitivity is a cell-mediated immune response, the results of our present study demonstrated that the production of dinitrochlorobenzene-specific antibodies by activated B cells played an indispensible role in the pathogenesis of dinitrochlorobenzene-induced CHS. These findings may provide new possibilities in the treatment of human contact hypersensitivity conditions.

DNFB-DNS hapten-induced colitis in mice should not be considered a model of inflammatory bowel disease5

“…Moreover, a clearly nonbiased cytokine response was induced after challenge with DNS, especially after a second contact with the hapten. Recently, the involvement of B cells and humoral Th2 response has also been described in cutaneous DTH responses induced by DNFB, 44,45 in contrast to that initially postulated, which favored the unique role of T cells and Th1 response in contact hypersensitivity reactions. 46 Therefore, the intestinal manifestation and the complexity of the immune response observed in the DNFB/ DNS mice model more than UC manifestations resemble the immune response detected in some food-hypersensitive patients where a mixture of IgE and non-IgE responses are observed, 47,48 and the response observed during some cases of irritable bowel syndrome, 49,50 a pathology that also requires experimental models for the evaluation of new pharmacological treatments.…”

Immunomodulatory effects of Pseudostellaria heterophylla (Miquel) Pax on regulation of Th1/Th2 levels in mice with atopic dermatitis

“…A previous study determined that CD4 + T cells increased in numbers in the AD-like skin lesions in DNCB-induced mice model (17). Accordingly, the elevation of CD4 expression in the dermis may suggest that Th1 and Th2 cells are involved (4).…”

Anti-dermatitis effects of oak wood vinegar on the DNCB-induced contact hypersensitivity via STAT3 suppression

“…Penetration of irritants or allergens into the living epidermal layers and keratinocyte membrane induces increased proliferation, which serves to remove the invading pathogens (Proksch et al, 2006). 2,4-Dinitrochlorobenzene (DNCB)-induced contact dermatitis in mice is a commonly used animal model for studying the pathogenesis of contact dermatitis (Zhang et al, 2009). STAT3 (signal transducers and activators of transcription 3) is a latent cytoplasmic protein involved in transmitting extracellular signals to the nucleus upon stimulation with interleukin-6 (IL-6), epidermal growth factor (EGF) and many other growth factors (Levy and Darnell, 2002).…”