Article Text

A2.27 The role of SYK in contact hypersensitivity
  1. JZ Csepregi1,
  2. T Németh1,
  3. FC Weber1,2,
  4. SF Martin2,
  5. A Mócsai1
  1. 1Department of Physiology, Semmelweis University School of Medicine and SE-MTA “Lendület” Inflammation Physiology Research Group, Budapest, Hungary
  2. 2Allergy Research Group, Department of Dermatology, University Medical Center Freiburg, Freiburg, Germany


Background and objectives Allergic contact dermatitis (ACD) is a common inflammatory skin disease, triggered by repeated exposure to contact allergens. ACD and its animal model, contact hypersensitivity (CHS), is a T-cell mediated delayed-type hypersensitivity reaction, which can be divided in sensitisation and elicitation phases. The Syk tyrosine plays important roles in several cell types known to be involved in the CHS response. Therefore, we tested whether Syk plays a role in CHS development, with particular emphasis on its importance in myeloid cells and its role in the sensitisation phase.

Materials and methods Bone marrow chimaeras with Syk–/– or μMT hematopoietic system were generated by fetal liver or bone marrow transplantation, respectively. Myeloid- and neutrophil-specific Syk deletion was achieved by crossing LysM-Cre and MRP8-Cre mice with Sykflox/flox animals (LysM-Cre Sykf/f and MRP8-Cre Sykf/f). CHS was triggered by sensitisation with the contact allergen TNCB, followed by elicitation with TNCB on the ears 5 days later. The role of Syk in the sensitisation phase was tested by in vitro T-cell re-stimulation with TNBS using IFNγ production as a functional readout.

Results While repeated exposure to TNCB triggered a robust increase in ear thickness in wild type mice or chimaeras, no such increase could be observed in Syk–/–chimaeras, indicating an important role for Syk in the CHS response. As Syk–/–chimaeras have no B-cells, we tested the possible contribution of these cells using a B-cell deficient mouse strain (μMT). There was no difference between the CHS response of wild type and B-cell deficient chimaeras, arguing against the role of B-cells in CHS development. Lineage-specific deletion studies revealed significant reduction in the ear thickness increase in LysM-Cre Sykf/f and MRP8-Cre Sykf/fmice, indicating an important role for Syk expression within the myeloid, and in particular within the neutrophil compartment. Syk deficiency significantly reduced the in vitro release of IFNγ by TNBS re-stimulated T-cells, indicating that Syk is important for the sensitisation phase of CHS.

Conclusions Our results show that Syk is indispensable for the CHS response and suggest a role for this kinase in the sensitisation phase. This is not due to the role of Syk in B-cells but, at least in part, to the expression of Syk in neutrophils.

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