{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:39:01Z","timestamp":1787776741748,"version":"build-2784847793"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T00:00:00Z","timestamp":1665100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013696","name":"Fondo Nacional de Ciencia y Tecnolog\u00eda","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013696","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Histamine (HA) is a potent mediator that plays a central role in inflammation and allergy, acting through four G-protein-coupled receptors (i.e. H<jats:sub>1<\/jats:sub>\u2013H<jats:sub>4<\/jats:sub>). HA is an accepted promoter of type 2 immunity in CD4<jats:sup>+<\/jats:sup>T cells during hypersensitivity. Previously, we demonstrated that HA can promote antigen cross-presentation, inducing the activation of antigen-specific CD8<jats:sup>+<\/jats:sup>T cells in an asthmatic murine model. Non-classical CD8+ T-cell profiles, such as Tc2 or Tc17, are associated with allergic disease persistence and chronicity. In this paper, we focus on the role of the H<jats:sub>3<\/jats:sub>receptor (H<jats:sub>3<\/jats:sub>R) and the H<jats:sub>4<\/jats:sub>receptor (H<jats:sub>4<\/jats:sub>R) in the development of allergic contact dermatitis. We were able to show that induction of the type 2 profiles associated with interleukin 13 production, both by CD4 and CD8 lymphocytes, depend on the interaction of HA with H<jats:sub>3<\/jats:sub>R and H<jats:sub>4<\/jats:sub>R. Blocking both receptors using the selective H<jats:sub>3<\/jats:sub>\/H<jats:sub>4<\/jats:sub>receptor antagonist thioperamide or the selective H<jats:sub>4<\/jats:sub>R ligand JNJ777120 reduces the inflammatory response, inducing an immunosuppressive profile associated with the increased proportion of FOXp3<jats:sup>+<\/jats:sup>regulatory T lymphocytes and CD11b<jats:sup>+<\/jats:sup>Gr-1<jats:sup>+<\/jats:sup>myeloid suppressor cells. Interestingly, in dendritic cells, only H<jats:sub>4<\/jats:sub>R blockade, and not H<jats:sub>3<\/jats:sub>R blockade, is capable of modulating most of the inflammatory effects observed in our model.<\/jats:p>","DOI":"10.3389\/fimmu.2022.999852","type":"journal-article","created":{"date-parts":[[2022,10,7]],"date-time":"2022-10-07T06:29:00Z","timestamp":1665124140000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Mechanisms of unconventional CD8 Tc2 lymphocyte induction in allergic contact dermatitis: Role of H3\/H4 histamine receptors"],"prefix":"10.3389","volume":"13","author":[{"given":"Julieta","family":"Alcain","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alejandra del Pilar","family":"Infante 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