Allergen-Specific Low Zone Tolerance Is Independent of MRP8/14-, TLR4-, TLR7-, and TLR9-Mediated Immune Processes Talkea Schmidt, Nadine Lorenz, Verena.

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Allergen-Specific Low Zone Tolerance Is Independent of MRP8/14-, TLR4-, TLR7-, and TLR9-Mediated Immune Processes Talkea Schmidt, Nadine Lorenz, Verena K. Raker, Maria I. Schmidgen, Karsten Mahnke, Alexander Enk, Johannes Roth, Kerstin Steinbrink Journal of Investigative Dermatology Volume 138, Issue 2, Pages 452-455 (February 2018) DOI: 10.1016/j.jid.2017.09.020 Copyright © 2017 The Authors Terms and Conditions

Figure 1 TLR4 and MRP14 are involved in the development of CHS but are not required for low zone tolerance to contact allergens. C57BL/6 WT, TLR4, and MRP14 knockout mice were tolerized with 0.45or 4.5μg TNCB or solvent treated (for CHS controls) for 10 times, respectively. Subsequently, CHS induction was performed. (a, b) Pooled data of ear swelling of two independent experiments are depicted (mean ± SD). (c, d) T cells were hapten-specific (TNBS) restimulated in vitro. The hapten-specific T-cell proliferation in vitro was demonstrated (mean value of triplicates in cpm, one representative out of two independent experiments). (e, f) Pooled data of the hapten-specific T-cell cytokine production (IFN-γ, IL-2) of two independent experiments are shown (mean ± SD) (n = 6–8 mice per experiment). *P < 0.05, **P < 0.01, ***P < 0.001, n.s. = not significant. CHS, contact hypersensitivity; KO, knockout; LZT, low zone tolerance; MRP, myeloid-related protein; SD, standard deviation; TLR, toll-like receptor; TNBS, 2,4,6-Trinitrobenzenesulfonic acid; TNCB, 2,3,6-trinitro-1-chlorobenzene; WT, wild-type. Journal of Investigative Dermatology 2018 138, 452-455DOI: (10.1016/j.jid.2017.09.020) Copyright © 2017 The Authors Terms and Conditions

Figure 2 TLR7- and TLR9-mediated signaling does not contribute to the development of LZT and CHS. TLR7 and TLR9 knockout and wild-type animals were tolerized (0.45 μg TNCB or 4.5 μg TNCB) or solvent treated, respectively. (a, b) Absolute increase in ear thickness was assessed after sensitization and challenge (mean ± SD). (c, d) T-cell proliferation after hapten-specific restimulation in vitro is shown (mean values of triplicates in cpm). One representative result of two experiments is demonstrated. (e, f). Hapten-specific T-cell cytokine production (IFN-γ, IL-2) after hapten-specific restimulation in vitro is depicted (pooled data of two independent experiments, mean ± SD) (n = 6–8 mice per experiment). *P < 0.05, **P < 0.01, ***P < 0.001, n.s. = not significant. CHS, contact hypersensitivity; KO, knockout; LZT, low zone tolerance; SD, standard deviation; TLR, toll-like receptor; TNCB, 2,3,6-trinitro-1-chlorobenzene; WT, wild-type. Journal of Investigative Dermatology 2018 138, 452-455DOI: (10.1016/j.jid.2017.09.020) Copyright © 2017 The Authors Terms and Conditions