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Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization
Alessandra Mazzoni, … , Alberto Visintin, David M. Segal
Alessandra Mazzoni, … , Alberto Visintin, David M. Segal
Published December 15, 2001
Citation Information: J Clin Invest. 2001;108(12):1865-1873. https://doi.org/10.1172/JCI13930.
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Histamine regulates cytokine production in maturing dendritic cells, resulting in altered T cell polarization

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Abstract

Atopic diseases such as allergy and asthma are characterized by increases in Th2 cells and serum IgE antibodies. The binding of allergens to IgE on mast cells triggers the release of several mediators, of which histamine is the most prevalent. Here we show that histamine, together with a maturation signal, acts directly upon immature dendritic cells (iDCs), profoundly altering their T cell polarizing capacity. We demonstrate that iDCs express two active histamine receptors, H1 and H2. Histamine did not significantly affect the LPS-driven maturation of iDCs with regard to phenotypic changes or capacity to prime naive T cells, but it dramatically altered the repertoire of cytokines and chemokines secreted by mature DCs. In particular, histamine, acting upon the H2 receptor for a short period of time, increased IL-10 production and reduced IL-12 secretion. As a result, histamine-matured DCs polarized naive CD4+ T cells toward a Th2 phenotype, as compared with DCs that had matured in the absence of histamine. We propose that the Th2 cells favor IgE production, leading to increased histamine secretion by mast cells, thus creating a positive feedback loop that could contribute to the severity of atopic diseases.

Authors

Alessandra Mazzoni, Howard A. Young, Jessica H. Spitzer, Alberto Visintin, David M. Segal

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Figure 2

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Histamine does not alter the APC function of DCs, but strongly regulates...
Histamine does not alter the APC function of DCs, but strongly regulates cytokine expression. (a) APC function. DCs were left untreated (medium alone), or were incubated overnight with histamine, LPS, or both (LPS + hist). Washed, irradiated DCs were added to allogeneic naive CD45RA+, CD4+ T cells, and T cell proliferation was assessed after 4 days by [3H]thymidine incorporation. One experiment of five performed is shown. (b) Cytokine and chemokine expression. iDCs were incubated with medium alone, or with medium containing histamine, LPS, or both. After 18 hours, total RNA was extracted and probed for cytokine/chemokine message expression using an RPA. Similar data were obtained in four separate experiments.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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