Efferocytosis capacities of blood monocyte-derived macrophages in systemic sclerosis
IMMUNOLOGY AND CELL BIOLOGY
Authors: Ballerie, Alice; Lescoat, Alain; Augagneur, Yu; Lelong, Marie; Morzadec, Claudie; Cazalets, Claire; Jouneau, Stephane; Fardel, Olivier; Vernhet, Laurent; Jego, Patrick; Lecureur, Valerie
Abstract
A defect in the apoptotic cell clearance (efferocytosis) by phagocytic cells may participate in autoimmunity and chronic inflammation. The mechanisms leading to the emergence of autoimmunity in systemic sclerosis (SSc) are still to be determined. In this study, the efferocytosis capacities of blood monocyte-derived macrophages (MDM) from patients with SSc were evaluated. Blood monocytes obtained from patients with SSc and healthy donors (HD) were differentiated in vitro into macrophages. The capacities of MDM to engulf CFSE+ apoptotic Jurkat human T lymphocytes were compared between SSc MDM and HD using flow cytometry. The expression of classical engulfing receptors in SSc MDM and HD MDM was also evaluated and their involvement in the modulation of efferocytosis was confirmed using a siRNA approach. The mean phagocytic index (PI) reflecting efferocytosis capacities of SSc MDM (PI = 19.3 +/- 3.0; n = 21) was significantly decreased in comparison with the PI of HD MDM (PI = 35.9 +/- 3.0; n = 31; P < 0.001). In comparison with HD, SSc MDM exhibited a downregulated expression of scavenger receptor (SR)-B1, SR-A1 and integrin beta 5 (ITG beta 5). In HD MDM, the extinction of these receptors was followed by a reduction of efferocytosis only for the repression of ITGb5, suggesting a possible selective role of this integrin in the impaired efferocytosis observed in SSc. As efferocytosis may be at the crossroads of inflammation, autoimmunity and fibrosis, in showing impaired efferocytosis capacities of blood MDM in SSc, our study offers new pathogenesis considerations for the involvement of macrophages in the autoimmune processes driving this disorder.
Evaluation of two promising genes from the target region of SSC13 with susceptibility towards the ETEC F4ac adhesion in pigs
ITALIAN JOURNAL OF ANIMAL SCIENCE
Authors: Liu, Yang; Hu, Zhengzheng; Yang, Chen; Wang, Lina; Wang, Shiwei; Wang, Wenwen; Zhang, Qin
Abstract
Enterotoxigenic Escherichia coli (ETEC) expressing F4 fimbria is the major pathogenic bacteria causing diarrhoea in neonatal and post-weaned piglets. Based on our previous GWAS results from 301 pigs in a two generation family-based population, two promising candidate genes (HEG1 and ITGB5) from a 0.65 Mb region on pig chromosome 13 for susceptibility to ETEC F4ac infection were investigated for the presence of possible causative mutations. A total of 23 polymorphisms in their coding regions were identified, and two previous uppermost GWAS significant SNPs (ALGA0072075; GenBank NC_010455.4:g.145009857 A > G) were also chosen for genotyping in the three pig breeds. The genotyping data and association analysis results showed that a C to T polymorphism in exon7, and a G to T polymorphism in exon14 of the HEG1 gene significant increased the effects on the ETEC F4ac adhesion traits (p = 2.853E-11; p = 1.410E - 09). Although the identified polymorphisms were not causal mutations, these results indicate that the HEG1 gene is an important adhesion molecule, and it could serve as a genetic marker for selecting ETEC F4ac-resistant pigs in breeding programmes.