TLRs, Treg, and B Cells, an Interplay of Regulation during Helminth Infection

Commonly described as masters of regulation parasitic helminth infections provide a fascinating insight into the complexity of our immune system. As with many other pathogens helminths have developed complex evasion strategies and the immune response of the host has to find a balance between eliciting severe damage to eliminate the parasite or limiting damage and thereby accepting the infection. Nevertheless, one should not forget that these infections still pose a serious public health problem and can elicit severe disfigurement or death in the individual. An interesting spin-off of helminth manipulation on host responses is the apparent prevention of autoimmune diseases or allergy although the actual mechanisms remain unclear. It is well known that Toll-like-receptors (TLR) and non-TLR PRRs play a critical role in initiating innate immune responses which in turn create appropriate adaptive immune reactions. Helminths comprise of a multitude of (glyco)-proteins and (glyco)-lipids and some have been shown to trigger TLR, or alter TLR-mediated responses. Such reactions of course alter adaptive immunity as well. This review will address the consequences of TLR-triggering by helminth antigens and the downstream effect on B cell and regulatory T cell (Treg) actions

Differential Induction of Ly6G and Ly6C Positive Myeloid Derived Suppressor Cells in Chronic Kidney and Liver Inflammation and Fibrosis

<div><p>CD11b⁺Gr1⁺ myeloid derived suppressor cells (MDSC) are known to be very potent suppressors of T cell immunity and can be further stratified into granulocytic MDSC and monocytic MDSC in mice based on expression of Ly6G or Ly6C, respectively. Here, using these markers and functional assays, we aimed to identify whether MDSC are induced during chronic inflammation leading to fibrosis in both kidney and liver and whether additional markers could more specifically identify these MDSC subsets. In an adenine-induced model of kidney inflammation/fibrosis suppressive Ly6G^pos MDSC were induced. The suppressive function within the Ly6G⁺ MDSC population was exclusively present in IFNγRβ expressing cells. In contrast, in chronic inflammation in the liver induced by bile duct ligation, suppressive capacity was exclusively present in the Ly6C^pos MDSC subset. Gene expression analyses confirmed the differential origins and regulation of those MDSC subsets. Additionally, depletion of MDSC in either kidney or liver fibrosis enhanced fibrosis markers, indicating a protective role for MDSC in organ fibrosis. Thus, our data demonstrate that during liver inflammation and kidney fibrosis MDSC with similar function arise bearing a distinct marker profile and arising from different cell populations.</p></div

New Aspects of Kidney Fibrosis–From Mechanisms of Injury to Modulation of Disease

Organ fibrogenesis is characterized by a common pathophysiological final pathway independent of the underlying progressive disease of the respective organ. This makes it particularly suitable as a therapeutic target. The Transregional Collaborative Research Center “Organ Fibrosis: From Mechanisms of Injury to Modulation of Disease” (referred to as SFB/TRR57) was hosted from 2009 to 2021 by the Medical Faculties of RWTH Aachen University and the University of Bonn. This consortium had the ultimate goal of discovering new common but also different fibrosis pathways in the liver and kidneys. It finally successfully identified new mechanisms and established novel therapeutic approaches to interfere with hepatic and renal fibrosis. This review covers the consortium's key kidney-related findings, where three overarching questions were addressed: (i) What are new relevant mechanisms and signaling pathways triggering renal fibrosis? (ii) What are new immunological mechanisms, cells and molecules that contribute to renal fibrosis?, and finally (iii) How can renal fibrosis be modulated

Fibrosis markers in the liver and kidney after all-trans-retinoic acid treatment.

<p>C57BL/6 mice underwent bile-duct ligation, were fed an adenine-enriched diet or as a control were left untreated. After 7 days mice were treated with 1g/L all-trans-retinoic acid (ATRA) in their drinking water (BDL: n = 7, Adenine: n = 4) or not (BDL: n = 8, adenine: n = 4)) for the remaining time until analysis. At day 14 (BDL and adenine feeding), total liver and kidney RNA was isolated for real-time PCR of fibrosis markers. Shown are mRNA expression levels for α-SMA, collagen IV, TGF-β and vimentin relative to the levels in non-treated mice (n = 3), which was set to 1. Data are depicted as mean +/- SEM. Significance was calculated by ANOVA. *p≤0.05, **p≤0.01, ***p≤0.001.</p