🔥Hot paper on #NonAlcoholicFattyLiverDisease
Title: Identifying Patients with Nonalcoholic Fatty Liver Disease in Primary Care: How and for What Benefit?
👥Authors: Dr. Andrew D. Schreine

The human immune system has a formidable arsenal of defenses to detect and eliminate threats. One of its most powerful guardians is the complement system — a dynamic network of proteins that tirelessly patrols our body, looking ever vigilantly for signs of infection or injury. In the presence of danger, these proteins spring into action, unleashing a cascade of inflammatory signals that mobilizes the body’s defenses to neutralize the threats.

#Autoimmunity | #Tregs | Differential roles of human CD4+ & CD8+ regulatory T cells in controlling self-reactive immune responses | Fundamental new insights by… | 10 comments on LinkedIn

Stem cells reside in specialized microenvironments, termed niches, at several different locations in tissues1–3. The differential functions of heterogeneous stem cells and niches are important given the increasing clinical applications of stem-cell transplantation and immunotherapy. Whether hierarchical structures among stem cells at distinct niches exist and further control aspects of immune tolerance is unknown. Here we describe previously unknown new hierarchical arrangements in haematopoietic stem cells (HSCs) and bone marrow niches that dictate both regenerative potential and immune privilege. High-level nitric oxide-generating (NOhi) HSCs are refractory to immune attack and exhibit delayed albeit robust long-term reconstitution. Such highly immune-privileged, primitive NOhi HSCs co-localize with distinctive capillaries characterized by primary ciliated endothelium and high levels of the immune-checkpoint molecule CD200. These capillaries regulate the regenerative functions of NOhi HSCs through the ciliary protein IFT20 together with CD200, endothelial nitric oxide synthase and autophagy signals, which further mediate immunoprotection. Notably, previously described niche constituents, sinusoidal cells and type-H vessels2–10 co-localize with less immune-privileged and less potent NOlow HSCs. Together, we identify highly immune-privileged, late-rising primitive HSCs and characterize their immunoprotective niches comprising specialized vascular domains. Our results indicate that the niche orchestrates hierarchy in stem cells and immune tolerance, and highlight future immunotherapeutic targets. Previously undescribed hierarchical arrangements in haematopoietic stem cells and their niches that mediate both regenerative potential and immune privilege are identified.

𝐂𝐞𝐥𝐥 𝐓𝐡𝐞𝐫𝐚𝐩𝐲 𝐋𝐚𝐧𝐝𝐬𝐜𝐚𝐩𝐞 𝐢𝐧 𝐀𝐮𝐭𝐨𝐢𝐦𝐦𝐮𝐧𝐢𝐭𝐲 🏄‍♂️

30 companies below categorised by 12 disease areas and other/undiscovered… | 26 comments on LinkedIn

The age of immunotherapy for type 1 diabetes is upon us! Thrilled by the opportunity to contribute to this review led by Remi Creusot at Columbia University!#immunologymatters #endt1d https://lnkd.in/eQ_E2j5d

I’m pleased to announce that our latest paper, “IgG autoantibodies in bullous pemphigoid induce a pathogenic MyD88-dependent pro-inflammatory response in keratinocytes,” has been published in Nature Communications! Our study reveals that keratinocytes actively drive the pathogenic inflammatory and proteolytic response in bullous pemphigoid by responding to BP-IgG autoantibodies via the MyD88 pathway, rather than acting as passive bystanders. This work advances our understanding of BP and may open up new avenues for targeted therapeutic strategies.

Grateful to my co-authors and all who supported this project.

Read the full article here: https://lnkd.in/eyCA3vZb
#bullouspemphigoid #autoimmunity #dermatology #immunology #research

Thrilled to share a huge work conducted with my mentor George Tsokos and friends and colleagues Antonios Kolios & Vasileios Kyttaris.

We critically review 20 years of advances in the treatment of #lupus and try to paint the landscape of its near future. As often, many treatments come from an improved understanding of the disease pathogenesis !

Open-access full text link : https://rdcu.be/ewD2J

Here we analyzed the relative contributions of CD4+ regulatory T cells expressing Forkhead box protein P3 (FOXP3) and CD8+ regulatory T cells expressing killer cell immunoglobulin-like receptors to the control of autoreactive T and B lymphocytes in human tonsil-derived immune organoids. FOXP3 and GZMB respectively encode proteins FOXP3 and granzyme B, which are critical to the suppressive functions of CD4+ and CD8+ regulatory T cells. Using CRISPR–Cas9 gene editing, we were able to achieve a reduction of ~90–95% in the expression of these genes. FOXP3 knockout in tonsil T cells led to production of antibodies against a variety of autoantigens and increased the affinity of influenza-specific antibodies. By contrast, GZMB knockout resulted in an increase in follicular helper T cells, consistent with the ablation of CD8+ regulatory T cells observed in mouse models, and a marked expansion of autoreactive CD8+ and CD4+ T cells. These findings highlight the distinct yet complementary roles of CD8+ and CD4+ regulatory T cells in regulating cellular and humoral responses to prevent autoimmunity. Here the authors use a tonsil organoid culture model system to investigate the roles of human CD4+ and CD8+ regulatory T cells in controlling self-reactive immune responses. CD4+ regulatory T cells were stronger regulators of autoreactive B cells, autoantibodies and antigen-specific antibody affinity, whereas CD8+ regulatory T cells predominantly controlled expansion of follicular helper cells and autoreactive CD4+ and CD8+ T cells.