Hernández-Chirlaque, CristinaGámez-Belmonte, ReyesOcón, BorjaMartínez-Moya, PatriciaWirtz, StefanSánchez de Medina, FermínMartínez-Augustin, Olga2023-01-252023-01-252017Hernández-Chirlaque C, Gámez-Belmonte R, Ocón B, Martínez-Moya P, Wirtz S, Sánchez de Medina F, et al. Tissue Non-specific Alkaline Phosphatase Expression is Needed for the Full Stimulation of T Cells and T Cell-Dependent Colitis. J Crohns Colitis. 2017 Jul 1;11(7):857-870http://hdl.handle.net/10668/10726Two 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.enAlkaline phosphataseRag1-/-T cellsanti-CD3colitisAlkaline PhosphataseAnimalsCell ProliferationColitisCytokinesEnzyme InhibitorsGene ExpressionHeterozygoteHomeodomain ProteinsLevamisoleLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutPhenylalaninePrimary Cell CultureRNA, MessengerSpleenT-LymphocytesTheophyllineresearch article28039309Restricted AccessLinfocitos TRatonesColitisCélulasFosfatasa Alcalina10.1093/ecco-jcc/jjw2221876-4479https://academic.oup.com/ecco-jcc/article-pdf/11/7/857/17940486/jjw222.pdf