Dipeptidyl peptidase IV (DPP4) deficiency increases Th1-driven allergic contact dermatitis.
ABSTRACT CD26 or dipeptidyl peptidase IV (DPP4) is known to be involved in several immunological processes and has recently been reported to play a crucial role in the allergic responses of the lungs.
To explore the impact of DPP4 on the allergic response of the skin.
Skin biopsies from patients suffering from atopic dermatitis (AD) and healthy controls were investigated for the expression of CD26/DPP4. Furthermore, the functional impact of CD26 was investigated in two models of contact hypersensitivity using CD26/DPP4-deficient and wild-type rats. Dinitrochlorobenzene (DNCB) was used to induce a T helper type 1 (Th1)-dominated inflammation and toluene-2,3-diisocyanate for a Th2-pronounced inflammation. The inflammatory responses were determined by histological quantification, flow cytometry [fluorescence-activated cell sorting (FACS)], and an enzyme-linked immunosorbant assay (ELISA).
CD26/DPP4-expression was up-regulated in the lesional skin biopsies of patients compared with healthy controls as well as in both models of contact hypersensitivity. However, in the more Th2-driven model, a reduced inflammatory skin response was found in CD26/DPP4-deficient rats, analogous to the effects observed recently in a rat model of asthma. In partial contrast, there was an aggravation of local skin inflammation in CD26/DPP4-deficient rats under conditions of Th1-like skin inflammation.
The up-regulation of CD26 in atopic dermatitis represents a new finding, which has also been seen in other inflammatory skin diseases. However, tissue expression of CD26/DPP4 in immunological skin response can either be beneficial or aggravating, depending on a possible Th1/Th2 shift. This might have consequences for humans suffering from diabetes mellitus treated by DPP4 inhibitors, who have eczematous skin diseases as a co-morbidity.
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ABSTRACT: Many disease models have shown that, within the species rat, different strains are differentially susceptible to asthma-induced inflammation depending on the genetic background. Likewise, CD26/DPPIV-deficiency in asthmatic F344 rats has been shown to result in a less pronounced inflammation and in increased Treg cell influx into the lung compared to wild-types. The aim of the present study was to investigate whether the genetic background of the animals interferes with CD26/DPPIV-deficiency in a model of allergic-like inflammation, or whether the deficiency per se is the predominant regulator of the inflammation. Therefore, we hypothesized that CD26/DPPIV-deficient Dark Agouti (DA) rats also exhibit a less pronounced ovalbumin (OVA)-induced inflammation compared to wild-types. After sensitisation with OVA, Al(OH)3 and heat-killed Bordetella pertussis bacilli, animals were challenged three times with 5% aerosolized OVA at intervals of 24 hours, i. e. on three consecutive days. 24 hours after the third challenge, animals were sacrificed and examined. In both wild-type and CD26/DPPIV-deficient rat groups, asthma induction led to 1) lung inflammation, 2) significantly increased eosinophil infiltration in the BALF, 3) significantly increased IgE serum levels, 4) a significant increase of inflammatory cytokines, 5) a significant increase of different T cell populations in the lungs and in their draining lymph nodes, as well as to 6) a significantly higher number of all T lymphocyte subtypes in the blood. Thus, the degree of the OVA-induced Th2-driven pulmonary inflammation was similarly pronounced in both wild-type and CD26/DPPIV-deficient DA rats.Immunobiology 11/2014; · 2.81 Impact Factor