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Inflammation is a beneficial host response to infection but can contribute to inflammatory disease if unregulated. The TH17 lineage of T helper (TH) cells can cause severe human inflammatory diseases. These cells exhibit both instability (they can cease to express their signature cytokine, IL-17A)1 and plasticity (they can start expressing cytokines typical of other lineages)1,2 upon in vitro re-stimulation. However, technical limitations have prevented the transcriptional profiling of pre- and post-conversion TH17 cells ex vivo during immune responses. Thus, it is unknown whether TH17 cell plasticity merely reflects change in expression of a few cytokines, or if TH17 cells physiologically undergo global genetic reprogramming driving their conversion from one T helper cell type to another, a process known as transdifferentiation3,4. Furthermore, although TH17 cell instability/plasticity has been associated with pathogenicity1,2,5, it is unknown whether this could present a therapeutic opportunity, whereby formerly pathogenic TH17 cells could adopt an anti-inflammatory fate. Here we used two new fate-mapping mouse models to track TH17 cells during immune responses to show that CD4+ T cells that formerly expressed IL-17A go on to acquire an anti-inflammatory phenotype. The transdifferentiation of TH17 into regulatory T cells was illustrated by a change in their signature transcriptional profile and the acquisition of potent regulatory capacity. Comparisons of the transcriptional profiles of pre- and postconversion TH17 cells also revealed a role for canonical TGF-β signalling and consequently for the aryl hydrocarbon receptor (AhR) in conversion. Thus, TH17 cells transdifferentiate into regulatory cells, and contribute to the resolution of inflammation. Our data suggest that TH17 cell instability and plasticity is a therapeutic opportunity for inflammatory diseases.

Referencia OEPM: P200302587.-- Fecha de solicitud: 05/11/2003.-- Titulares: Universidad Autónoma de Madrid, Consejo Superior de Investigaciones Científicas (CSIC) y Pilar Lauzurica Gómez.-- Patente de invención PV200300252: http://hdl.handle.net/10261/4934, Mejoras introducidas en la patente de invención nº PV200300252 correspondiente a la utilización de una cantidad efectiva de una molécula de activación temprana, la cual es una molécula de anticuerpo antagonista anti-CD69 seleccionado de entre una molécula de anticuerpo humanizada anti-CD69, una molécula de anticuerpo humana anti-CD69, una molécula de anticuerpo quimérica anti-CD69 y una molécula de anticuerpo deinmunizada anti-CD69 para la fabricación de un medicamento destinado al tratamiento de un sujeto que necesite, o pueda beneficiarse de, una respuesta inmune aumentada, en donde dicho antagonista disminuye la señalización por la molécula de activación temprana o reduce la interacción de la molécula de activación temprana con un ligando de dicha molécula de activación temprana.

Solicitud de patente Fecha de presentación: 31/01/2003.-- Solicitantes: Universidad Autónoma de Madrid (UAM), Consejo Superior de Investigaciones Científicas (CSIC).-- Mejoras introducidas en esta patente de invención: http://hdl.handle.net/10261/5227, La presente invención se refiere a la utilización de una cantidad efectiva de un antagonista de CD69 seleccionado del grupo: una molécula de anticuerpo humanizada anti-CD69, una molécula de anticuerpo humana anti-CD69 , una molécula de anticuerpo quimérica anti-CD69 y una molécula de anticuerpo desinmunizada anti-CD69 para la fabricación de un medicamento destinado al tratamiento de un sujeto que necesite o pueda beneficiarse de una respuesta inmune aumentada.

Fecha de presentación internacional: 02.02.2004. - Titular: Consejo Superior de Investigaciones Científicas (CSIC), Disclosed are methods of treating subjects having disorders or conditions characterized by an unwanted immune response including administering an effective amount of an early activation molecule agonist, antagonist or depletor, to the subject. Human monoclonal antibodies specific to the early activation molecules, and methods of use, are also disclosed.