title: Dipeptidyl peptidase IV (DPP4) deficiency increases Th1-driven allergic contact dermatitis.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To explore the impact of DPP4 on the allergic response of the skin.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Tasic
authors.forename: W
authors.initials: W
authors.lastname: Bäumer
authors.forename: A
authors.initials: A
authors.lastname: Schmiedl
authors.forename: F
authors.initials: F
authors.lastname: Schwichtenhövel
authors.forename: R
authors.initials: R
authors.lastname: Pabst
authors.forename: U
authors.initials: U
authors.lastname: Raap
authors.forename: S
authors.initials: S
authors.lastname: von Hörsten
authors.forename: M
authors.initials: M
authors.lastname: Stephan
mesh_terms: D000818:Animals; D020296:Animals, Congenic; D001706:Biopsy; D002478:Cells, Cultured; D017449:Dermatitis, Allergic Contact / Q000276:immunology*; D003876:Dermatitis, Atopic / Q000276:immunology; D018819:Dipeptidyl Peptidase 4 / Q000172:deficiency* / Q000276:immunology / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D051381:Rats; D012882:Skin Tests; D018417:Th1 Cells / Q000276:immunology*
chemical_list: D018819:Dipeptidyl Peptidase 4