Identification of a Novel Alternatively Spliced Form of Inflammatory Regulator SWAP-70-Like Adapter of T Cells

Abstract

Activation of naive CD4+ T cells results in the development of several distinct subsets of effector Th cells, including Th2 cells that play a pivotal role in allergic inflammation and helminthic infections. SWAP-70-like adapter of T cells (SLAT), also known as Def6 or IBP, is a guanine nucleotide exchange factor for small GTPases, which regulates CD4+ T cell inflammatory responses by controlling Ca2+/NFAT signaling. In this study, we have identified a novel alternatively spliced isoform of SLAT, named SLAT2, which lacks the region encoded by exons 2–7 of the Def6 gene. SLAT2 was selectively expressed in differentiated Th2 cells after the second round of in vitro stimulation, but not in differentiated Th1, Th17, or regulatory T (Treg) cells. Functional assays revealed that SLAT2 shared with SLAT the ability to enhance T cell receptor- (TCR-) mediated activation of NFAT and production of IL-4 but was unable to enhance TCR-induced adhesion to ICAM-1. Ectopic expression of SLAT2 or SLAT in Jurkat T cells resulted in the expression of distinct forms of filopodia, namely, short versus long ones, respectively. These results demonstrate that modulating either SLAT2 or SLAT protein expression could play critical roles in cytokine production and actin reorganization during inflammatory immune responses.

Th17 cells differentiated with mycelial membranes of Candida albicans prevent oral candidiasis

“…CD4 + T cells were magnetically isolated from lymph nodes and/or spleen cells by a previously described method (Hashimoto et al. 2017 ). Magnetic sorting was performed using Dynabeads Mouse CD4 (Invitrogen, Thermo Fisher Scientific, MA, USA) followed by treatment with DETACHaBEAD Mouse CD4 (Invitrogen).…”

Pathobiont-responsive Th17 cells in gut-mouth axis provoke inflammatory oral disease and are modulated by intestinal microbiome

“…In vitro stimulation of CD4 + T cells was performed as descried in previous reports (Hashimoto et al, 2017;Tasaki al., 2018). Briefly, bone marrow (BM) cells were harvested from femurs and tibias of B6 mice.…”