Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation

Marilena Lapilla, Barbara Gallo, Marianna Martinello, Claudio Procaccini, Massimo Costanza, Silvia Musio, Barbara Rossi, Stefano Angiari, Cinthia Farina, Lawrence Steinman, Giuseppe Matarese, Gabriela Constantin, Rosetta Pedotti

Research output: Contribution to journalArticle

Abstract

Histamine may contribute to the pathology of MS and its animal model EAE. We explored the effects of histamine and specific HR agonists on activation and migratory capacity of myelin-autoreactive T cells. We show that histamine in vitro inhibits proliferation and IFN-γ production of mouse T cells activated against PLP139-151. These effects were mimicked by the H1R agonist HTMT and the H2R agonist dimaprit and were associated with reduced activation of ERK1/2 kinase and with increased levels of cell cycle inhibitor p27Kip-1, both involved in T cell proliferation and anergy. H1R and H2R agonists reduced spontaneous and chemokine-induced adhesion of autoreactive T cells to ICAM-1 in vitro and blocked firm adhesion of these cells in inflamed brain microcirculation in vivo. Thus histamine, through H1R and H2R, inhibits activation of myelin-autoreactive T cells and their ability to traffic through the inflamed BBB. Strategies aimed at interfering with the histamine axis might have relevance in the therapy of autoimmune disease of the CNS.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalJournal of Leukocyte Biology
Volume89
Issue number2
DOIs
Publication statusPublished - Feb 2011

Fingerprint

Adhesiveness
Microcirculation
Histamine
T-Lymphocytes
Brain
Myelin Sheath
Dimaprit
Mitogen-Activated Protein Kinase 3
Intercellular Adhesion Molecule-1
Chemokines
Cell Adhesion
Autoimmune Diseases
Cell Cycle
Animal Models
Cell Proliferation
Pathology

Keywords

  • Autoimmunity
  • Chemokine
  • Cytokine
  • EAE
  • MS

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

Cite this

Lapilla, M., Gallo, B., Martinello, M., Procaccini, C., Costanza, M., Musio, S., ... Pedotti, R. (2011). Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation. Journal of Leukocyte Biology, 89(2), 259-267. https://doi.org/10.1189/jlb.0910486

Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation. / Lapilla, Marilena; Gallo, Barbara; Martinello, Marianna; Procaccini, Claudio; Costanza, Massimo; Musio, Silvia; Rossi, Barbara; Angiari, Stefano; Farina, Cinthia; Steinman, Lawrence; Matarese, Giuseppe; Constantin, Gabriela; Pedotti, Rosetta.

In: Journal of Leukocyte Biology, Vol. 89, No. 2, 02.2011, p. 259-267.

Research output: Contribution to journalArticle

Lapilla, M, Gallo, B, Martinello, M, Procaccini, C, Costanza, M, Musio, S, Rossi, B, Angiari, S, Farina, C, Steinman, L, Matarese, G, Constantin, G & Pedotti, R 2011, 'Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation', Journal of Leukocyte Biology, vol. 89, no. 2, pp. 259-267. https://doi.org/10.1189/jlb.0910486
Lapilla, Marilena ; Gallo, Barbara ; Martinello, Marianna ; Procaccini, Claudio ; Costanza, Massimo ; Musio, Silvia ; Rossi, Barbara ; Angiari, Stefano ; Farina, Cinthia ; Steinman, Lawrence ; Matarese, Giuseppe ; Constantin, Gabriela ; Pedotti, Rosetta. / Histamine regulates autoreactive T cell activation and adhesiveness in inflamed brain microcirculation. In: Journal of Leukocyte Biology. 2011 ; Vol. 89, No. 2. pp. 259-267.
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