Dendritic cell SIRPα regulates homeostasis of dendritic cells in lymphoid organs

Signal regulatory protein α (SIRPα), an immunoglobulin superfamily protein that is expressed predominantly in myeloid lineage cells such as dendritic cells (DCs) or macrophages, mediates cell–cell signaling. In the immune system, SIRPα is thought to be important for homeostasis of DCs, but it remains unclear whether SIRPα intrinsic to DCs is indeed indispensable for such functional role. Thus, we here generated the mice, in which SIRPα was specifically ablated in CD11c⁺ DCs (Sirpa^ΔDC). Sirpa^ΔDC mice manifested a marked reduction of CD4⁺ CD8α^– conventional DCs (cDCs) in the secondary lymphoid organs, as well as of Langerhans cells in the epidermis. Such reduction of cDCs in Sirpa^ΔDC mice was comparable to that apparent with the mice, in which SIRPα was systemically ablated. Expression of SIRPα in DCs was well correlated with that of either endothelial cell‐selective adhesion molecule (ESAM) or Epstein–Barr virus‐induced molecule 2 (EBI2), both of which were also implicated in the regulation of DC homeostasis. Indeed, ESAM⁺ or EBI2⁺ cDCs were markedly reduced in the spleen of Sirpa^ΔDC mice. Thus, our results suggest that SIRPα intrinsic to CD11c⁺ DCs is essential for homeostasis of cDCs in the secondary lymphoid organs and skin.     

Clinical phenotypes of spinal muscular atrophy patients with hybrid SMN gene

BackgroundSpinal muscular atrophy (SMA) is a neuromuscular disease caused by homozygous deletion of SMN1 exons 7 and 8. However, exon 8 is retained in some cases, where SMN2 exon 7 recombines with SMN1 exon 8, forming a hybrid SMN gene. It remains unknown how the hybrid SMN gene contribute to the SMA phenotype.MethodWe analyzed 515 patients with clinical suspicion for SMA. SMN1 exons 7 and 8 deletion was detected by PCR followed by enzyme digestion. Hybrid SMN genes were further analyzed by nucleotide sequencing. SMN2 copy number was determined by real-time PCR.ResultsSMN1 exon 7 was deleted in 228 out of 515 patients, and SMN1 exon 8 was also deleted in 204 out of the 228 patients. The remaining 24 patients were judged to carry a hybrid SMN gene. In the patients with SMN1 exon 7 deletion, the frequency of the severe phenotype was significantly lower in the patients with hybrid SMN gene than in the patients without hybrid SMN gene. However, as for the distribution of SMN2 exon 7 copy number among the clinical phenotypes, there was no significant difference between both groups of SMA patients with or without hybrid SMN gene.ConclusionHybrid SMN genes are not rare in Japanese SMA patients, and it appears to be associated with a less severe phenotype. The phenotype of patients with hybrid SMN gene was determined by the copy number of SMN2 exon 7, as similarly for the patients without hybrid SMN gene.     

Vascular remodeling and plaque composition between focal and diffuse coronary lesions assessed by intravascular ultrasound

Coronary remodeling and plaque composition were compared between focal and diffuse coronary lesions. Negative remodeling and fibrous and calcified plaque compositions contribute to stenosis development in diffuse lesions more frequently than in focal lesions.