A network-based analysis of the late-phase reaction of the skin

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A network-based analysis of the late-phase reaction of the skin. / Benson, Mikael; Langston, Michael A.; Adner, Mikael; Andersson, Bengt; Torinssson-Naluai, Asa; Cardell, Lars-Olaf.

In: Journal of Allergy and Clinical Immunology, Vol. 118, No. 1, 2006, p. 220-225.

Research output: Contribution to journalArticle

Harvard

Benson, M, Langston, MA, Adner, M, Andersson, B, Torinssson-Naluai, A & Cardell, L-O 2006, 'A network-based analysis of the late-phase reaction of the skin', Journal of Allergy and Clinical Immunology, vol. 118, no. 1, pp. 220-225. https://doi.org/10.1016/j.jaci.2006.03.006

APA

Benson, M., Langston, M. A., Adner, M., Andersson, B., Torinssson-Naluai, A., & Cardell, L-O. (2006). A network-based analysis of the late-phase reaction of the skin. Journal of Allergy and Clinical Immunology, 118(1), 220-225. https://doi.org/10.1016/j.jaci.2006.03.006

CBE

Benson M, Langston MA, Adner M, Andersson B, Torinssson-Naluai A, Cardell L-O. 2006. A network-based analysis of the late-phase reaction of the skin. Journal of Allergy and Clinical Immunology. 118(1):220-225. https://doi.org/10.1016/j.jaci.2006.03.006

MLA

Vancouver

Benson M, Langston MA, Adner M, Andersson B, Torinssson-Naluai A, Cardell L-O. A network-based analysis of the late-phase reaction of the skin. Journal of Allergy and Clinical Immunology. 2006;118(1):220-225. https://doi.org/10.1016/j.jaci.2006.03.006

Author

Benson, Mikael ; Langston, Michael A. ; Adner, Mikael ; Andersson, Bengt ; Torinssson-Naluai, Asa ; Cardell, Lars-Olaf. / A network-based analysis of the late-phase reaction of the skin. In: Journal of Allergy and Clinical Immunology. 2006 ; Vol. 118, No. 1. pp. 220-225.

RIS

TY - JOUR

T1 - A network-based analysis of the late-phase reaction of the skin

AU - Benson, Mikael

AU - Langston, Michael A.

AU - Adner, Mikael

AU - Andersson, Bengt

AU - Torinssson-Naluai, Asa

AU - Cardell, Lars-Olaf

PY - 2006

Y1 - 2006

N2 - Background: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. Objective: We sought to identify disease-associated pathways in the LPR using a network-based analysis. Methods: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. Results: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from TH2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of TH2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. Conclusion: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4-dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. Clinical implications: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.

AB - Background: The late-phase reaction (LPR) of the skin is an in vivo model of allergic inflammation. Objective: We sought to identify disease-associated pathways in the LPR using a network-based analysis. Methods: The LPR was examined by means of DNA microarray analysis of skin biopsy specimens from 10 patients with allergic rhinitis and 10 healthy control subjects. The results were further analyzed in 2 different materials consisting of nasal fluids and allergen-challenged CD4(+) T cells from patients with allergic rhinitis. Results: The DNA microarray analysis revealed several genes of known relevance to allergy. The eosinophil marker Charcot-Leyden crystal protein (CLC) that encodes Charcot-Leyden crystal protein differed most in expression. A network-based analysis showed upregulation of IL-4- and CCL4-dependent pathways and downregulation of a TGF-beta-induced pathway. CCL4 is expressed by CD4(+) T cells and chemotactic for eosinophils. We hypothesized that allergen induces release of CCL4 from TH2 cells and that this contributes to influx of eosinophils. Further analysis showed increase of CCL4 protein in nasal fluids from allergic patients during the season. Allergen challenge of PBMCs resulted in proliferation of TH2 cells and increased production of CCL4 in CD4(+) T cells from allergic patients. An analysis of the DNA microarray data revealed a significant correlation between CCL4 and the eosinophil marker CLC. Conclusion: A network-based analysis of the LPR showed increased activity of IL-4- and CCL4-dependent pathways and downregulation of the TGF-beta-induced pathway. Allergen-induced release of CCL4 from T(H)2 cells might contribute to influx of eosinophils during the LPR. Clinical implications: Involvement of multiple interacting pathways indicates that it might be difficult to identify one single mediator as a biomarker or drug target in allergic inflammation.

KW - late-phase reaction

KW - DNA microarrays

KW - gene expression

U2 - 10.1016/j.jaci.2006.03.006

DO - 10.1016/j.jaci.2006.03.006

M3 - Article

VL - 118

SP - 220

EP - 225

JO - Journal of Allergy and Clinical Immunology

T2 - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

SN - 1097-6825

IS - 1

ER -