Endoplasmic Reticulum Stress Response Mediator IRE-1α Promotes Host Dendritic Cells in Graft-versus-Host Disease Development.

Allogeneic hematopoietic cell transplantation is an effective treatment for hematologic malignancies, but the complications such as graft-versus-host disease (GVHD) can limit its benefit. The conditioning regimens before transplant, including chemotherapy or irradiation, can trigger endoplasmic reticulum stress. IRE-1α is a major endoplasmic reticulum stress mediator that can further activate both spliced XBP-1 (XBP-1s) and regulated IRE-1-dependent decay (RIDD). IRE-1α-XBP-1s signaling controls dendritic cell (DC) differentiation and Ag presentation, crucial in GVHD progression. In this study, we used DC-specific XBP-1-deficient mice as donors or recipients and observed that XBP-1s was crucial for host DCs in the induction of GVHD but dispensable for the graft-versus-leukemia response. To specifically target IRE-1α in the host, we treated recipient mice with the IRE-1α inhibitor B-I09 for 3 d prior to bone marrow transplantation, which significantly suppressed GVHD development while maintaining the graft-versus-leukemia effect. XBP-1-deficient or BI09-treated recipients showed reduced DC survival after irradiation and bone marrow transplantation. Inhibition of IRE-1α also led to a reduction in DC alloreactivity, subsequently decreasing the proliferation and activation of allogeneic T cells. With further study using RIDD-deficient DCs, we observed that RIDD was also required for optimal DC activation. Taken together, XBP-1s and RIDD both promote host DC survival and alloreactivity that contribute to GVHD development.

Characterization of radial artery perforation patterns using optical coherence tomography.

BACKGROUND: The characterization of radial artery perforation (RAP) patterns using optical coherence tomography (OCT) has not been well established. This study aimed to identify the characteristic RAP patterns in patients diagnosed through post-procedural OCT examination. METHODS: This retrospective study included 1936 consecutive patients who underwent radial artery (RA) OCT following OCT-guided transradial coronary intervention (TRI) from January 2016 to July 2022. Data regarding RAP characteristics were collected through OCT, including the perforation site as well as dimensions such as the length, width, and arc. Furthermore, RAP types were classified as small or large perforations, with a cut-off arc value of ≤90°. RESULTS: RAP, as identified by RA angiography (RAA) during TRI and on post-procedural OCT, was found in 16 out of 1936 patients (0.83 %). RA OCT imaging showed that the median distance between the RA ostium and the perforation site, the perforation length, width, and arc were 30.6 (14.4-42.2) mm, 1.55 (1.03-1.92) mm, 0.74 (0.60-1.14) mm, and 42.5 (25.0-58.1) °, respectively. Small perforations (arc ≤90°) were observed in 14 out of the 16 (87.5 %) patients with RAP. Post-procedural RAA revealed that 15 out of the 16 (93.7 %) patients with RAP had sealed perforations, with the remaining patient requiring external compression. CONCLUSIONS: Our findings demonstrated that RAP is uncommon during TRI, with clearly defined characteristic patterns on OCT. Most RAPs are small and tend to spontaneous seal through catheter tamponade.