Mucosal-associated invariant T cells contribute to suppression of inflammatory myeloid cells in immune-mediated kidney disease.

Mucosal-associated invariant T (MAIT) cells have been implicated in various inflammatory diseases of barrier organs, but so far, their role in kidney disease is unclear. Here we report that MAIT cells that recognize their prototypical ligand, the vitamin B2 intermediate 5-OP-RU presented by MR1, reside in human and mouse kidneys. Single cell RNAseq analysis reveals several intrarenal MAIT subsets, and one, carrying the genetic fingerprint of tissue-resident MAIT17 cells, is activated and expanded in a murine model of crescentic glomerulonephritis (cGN). An equivalent subset is also present in kidney biopsies of patients with anti-neutrophil cytoplasmatic antibody (ANCA)-associated cGN. MAIT cell-deficient MR1 mice show aggravated disease, whereas B6-MAITCAST mice, harboring higher MAIT cell numbers, are protected from cGN. The expanded MAIT17 cells express anti-inflammatory mediators known to suppress cGN, such as CTLA-4, PD-1, and TGF-ß. Interactome analysis predicts CXCR6 - CXCL16-mediated cross-talk with renal mononuclear phagocytes, known to drive cGN progression. In line, we find that cGN is aggravated upon CXCL16 blockade. Finally, we present an optimized 5-OP-RU synthesis method which we apply to attenuating cGN in mice. In summary, we propose that CXCR6+ MAIT cells might play a protective role in cGN, implicating them as a potential target for anti-inflammatory therapies.

Generation of an alpaca serum that induces immune-mediated crescentic glomerulonephritis in mice.

Crescentic glomerulonephritis (cGN) is the most aggressive form of glomerulonephritis in humans. A widely studied mouse model is induced by sheep or rabbit antisera raised against murine renal cortical antigens. We here, report that Alpaca readily produce ample amounts of antisera that induces pathology in mice, resembling human disease regarding crescent formation, proteinuria, infiltrating immune cells and a significant Th1, but not Th17 immune response. Alpaca antiserum did not cause end-stage kidney failure, neither in a passive nor in an accelerated experimental setting, which may be advantageous for long term studies of crescentic glomerulonephritis.

Stability and Change in Intergenerational Family Relations Across Two Decades: Findings From the German Ageing Survey, 1996-2014.

OBJECTIVES: Using high-quality data from Germany, this study aims to contribute to the yet little knowledge about possible changes in adult parent-child relationships within countries over time. METHOD: Analyzing 13,106 interviews from four rounds of the German Ageing Survey (DEAS), covering the period 1996-2014, we monitor stability and change in four dimensions of adult parent-child relationships, namely geographic proximity, frequency of contact, emotional closeness, and exchange of support. RESULTS: We observed a continuous decrease in parent-child geographic proximity between 1996 and 2008, but no further increase in distance thereafter. There was no change in intergenerational frequency of contact or emotional closeness between 1996 and 2014. Parents' propensity to support a child tended to decrease in the early 2000s, with signs of recovery in 2014. Whereas parents' receipt of material support from children remained stable, their probability to receive instrumental support declined between 1996 and 2008, but not any further thereafter. DISCUSSION: Temporal patterns of intergenerational solidarities within countries might be characterized simultaneously by stability and change, where increasing geographic mobility, for example, is paralleled by continuous family cohesion. Family members appear to react to variations in social and economic circumstances with behavioral changes allowing them to maintain high levels of overall intergenerational solidarity.

Longevity of chilled canine semen comparing different extenders.

The use of chilled semen has raised increased interest due to several reasons. The present study compares 3 extenders for chilling of canine semen over a 10 days storage period. Sperm rich fractions (n = 30) were divided into three aliquots and diluted with (a) a self-made tris-egg yolk extender (TEY), (b) the commercial CaniPRO™Chill 10 (CP, Minitüb, Germany) and (c) the Uppsala Equex-2 system (UpA+B): UpA+B (n = 12) or UpA (n = 18). % of totally and progressively motile sperm using computer-assisted sperm analysis (CASA, TM, PM), % live, membrane intact spermatozoa (SYBR-14/propidium iodide), % morphologically abnormal sperm, % acrosomal changes (Spermac(®)) and % membrane intact sperm (HOS test) were examined on days 0, 1, 2, 3, 5, 7 and 10. Semen quality significantly decreased during storage with significantly lower motility and lower % of live, membrane intact spermatozoa in UpA+B diluted samples. Although quality of samples chilled with TEY, CP and UpA was similar within the first 3 days, only TEY and CP revealed good results in preserving semen quality over 10 days with significantly higher PM, CASA motility parameters and % morphologically normal sperm in CP-chilled samples (each p<0.05).