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Title: Tissue Non-specific Alkaline Phosphatase Expression is Needed for the Full Stimulation of T Cells and T Cell-Dependent Colitis.
Authors: Hernández-Chirlaque, Cristina
Gámez-Belmonte, Reyes
Ocón, Borja
Martínez-Moya, Patricia
Wirtz, Stefan
Sánchez de Medina, Fermín
Martínez-Augustin, Olga
Keywords: Alkaline phosphatase;Rag1-/-;T cells;anti-CD3;colitis
metadata.dc.subject.mesh: Alkaline Phosphatase
Cell Proliferation
Enzyme Inhibitors
Gene Expression
Homeodomain Proteins
Lymphocyte Activation
Mice, Inbred C57BL
Mice, Knockout
Primary Cell Culture
RNA, Messenger
Issue Date: 2017
Abstract: Two alkaline phosphatase isoforms, intestinal [IAP] and tissue non-specific alkaline phosphatase [TNAP], are coexpressed in mouse colon, with the latter predominating in colitis. We aimed to examine the role of TNAP in T lymphocytes, using heterozygous TNAP+/- mice [as TNAP-/- mice are non-viable]. In vitro primary cultures and in vivo T cell models using TNAP+/- mice were used. Stimulated splenocytes [lipopolysaccharide and concanavalin A] and T lymphocytes [concanavalin A and a-CD3/a-CD28] showed a decreased cytokine production and expression when compared with wild-type [WT] cells. Decreased T cell activation was reproduced by the TNAP inhibitors levamisole, theophylline, and phenylalanine in WT cells. Intraperitoneal administration of anti-CD3 in vivo resulted in reduced plasma cytokine levels, and decreased activation of splenocytes and T cells ex vivo in TNAP+/- mice. We further tested the hypothesis that TNAP expressed in T lymphocytes is involved in T cell activation and inflammation, using the lymphocyte transfer model of colitis. Rag1-/- mice were transferred with T naïve cells [CD4+ CD62L+] from TNAP+/- or WT mice and developed colitis, which was attenuated in the group receiving TNAP+/- cells. Compared with WT, T cells from TNAP+/- mice showed a decreased capacity for proliferation, with no change in differentiation. Our results offer clear evidence that TNAP modulates T lymphocyte function and specifically T cell-dependent colitis. This was associated with distinct changes in the type of TNAP expressed, probably because of changes in glycosylation.
metadata.dc.identifier.doi: 10.1093/ecco-jcc/jjw222
Appears in Collections:Producción 2020

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