Extracellular vesicles at the immune–metabolic crossroads of Hashimoto’s thyroiditis and diabetes mellitus

Exosome in Hashimoto’s thyroiditis: from pathogenesis to diagnostic and therapeutic potential

Impact of dermatology targeted immunotherapies on autoimmune thyroid diseases: cytokine-network crosstalk and thyroid safety

Autoimmune thyroid diseases (AITDs), including Hashimoto’s thyroiditis (HT) and Graves’ disease (GD), affect approximately 2–5% of the global population. They are the most common organ-specific autoimmune disorders worldwide. Growing epidemiological and immunological evidence indicates that AITDs frequently coexist with immune-mediated dermatological diseases. These include atopic dermatitis (AD), psoriasis, alopecia areata (AA), vitiligo, and chronic spontaneous urticaria (CSU). Targeted immunotherapies have become central to the treatment of many immune-mediated skin diseases. Although these therapies are designed to act on specific immune pathways, they may also exert broader systemic immunomodulatory effects. However, thyroid function and thyroid autoantibodies are not routinely assessed in patients with immune-mediated dermatological conditions. This is also true for some patients with known or suspected AITDs. In this narrative review, we summarize the immunological overlap between cutaneous inflammation and autoimmune thyroid disease. We also discuss thyroid-related evidence for IL-4Rα inhibitors, IL-17 inhibitors, JAK inhibitors, IL-12/23 inhibitors, and immune checkpoint inhibitors (ICIs). Current evidence suggests that ICIs have the strongest established association with thyroid dysfunction. In contrast, the thyroid-related effects of dupilumab and ustekinumab are supported mainly by rare case reports. IL-17 inhibitors and selective IL-23p19 inhibitors may theoretically attenuate thyroid inflammatory pathways. However, this possibility has not yet been confirmed in clinical studies. Based on the available evidence, we propose a risk-stratified approach to thyroid surveillance across targeted immunotherapies. Routine thyroid monitoring is most strongly supported for ICIs. For patients at increased thyroid risk, selective assessment of thyroid function and thyroid autoantibodies may also be considered during treatment with dupilumab or ustekinumab. For oral JAK inhibitors, monitoring may be particularly relevant before treatment, during therapy, and after discontinuation because of the potential for immune rebound. Prospective studies are needed to define which patient subgroups would benefit most from thyroid surveillance during targeted immunotherapy.

Lactobacillus in autoimmune thyroid diseases: benefit or risk?

Overall, Lactobacillus-related interventions remain investigational, and future studies should prioritize standardized strain identification, disease-specific mechanisms, long-term safety, and well-designed clinical trials.

Metabolic switch: lymphocytes and the onset of T-cell-mediated autoimmunity.

T cell-mediated autoimmune diseases, including multiple sclerosis (MS), rheumatoid arthritis (RA), and type 1 diabetes (T1D), are being increasingly recognized as disorders driven not only by immune dysregulation but also by profound metabolic reprogramming in lymphocytes. Emerging evidence from the field of immunometabolism reveals that altering the balance between oxidative phosphorylation (OXPHOS) and aerobic glycolysis, along with enhancing fatty acid synthesis and dysregulated glutamine metabolism, critically shapes lymphocyte activation, differentiation, and pathogenicity. Here, we review the metabolic pathways that regulate T cells and B cells. We discuss how changes in glucose, lipid, and mitochondrial metabolism influence immune responses that lead to chronic inflammation and autoimmunity in MS, RA, and T1D. Interestingly, similar immunometabolic changes, such as increased glycolysis, mitochondrial dysfunction, and mTOR signaling, have been identified in another autoimmune disorder, systemic lupus erythematosus (SLE). Connecting metabolic dysregulation to immune tolerance failure, this review highlights immunometabolism as a key mechanism in autoimmunity. Immunometabolic pathways represent a new avenue for precision immunotherapy, although challenges persist in targeting cells specifically without systemic toxicity. Understanding these metabolic adaptations and epigenetic-metabolic crosstalk will be essential for translating these insights into next-generation therapies.

Dendritic Cells as Immunometabolic Regulatory Nodes in Diabetes: Molecular Mechanisms and Therapeutic Reprogramming

Diabetes mellitus comprises a group of heterogeneous metabolic disorders characterized by persistent hyperglycemia, progressive β-cell dysfunction, and multi-organ complications. Although type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) have distinct pathogenic origins, both involve immune dysregulation, tissue stress, release of danger signals, and chronic inflammation. Dendritic cells (DCs), as antigen-presenting cells, integrate innate immune sensing, antigen presentation, cytokine production, T-cell regulation, and peripheral immune tolerance, placing them at a critical interface between autoimmunity and metabolic inflammation. In T1DM, DCs contribute to β-cell autoantigen presentation, tolerance breakdown, autoreactive T-cell activation, and insulitis amplification. In T2DM, DCs may contribute to adipose tissue inflammation, hepatic immunometabolic crosstalk, β-cell stress, vascular inflammation, and immune remodeling associated with diabetes-related complications. Here, we review the disease-specific roles of DC subsets in T1DM and T2DM and discuss shared molecular mechanisms, including pattern-recognition receptor signaling, metabolic reprogramming, inflammasome activation, cytokine networks, and the shift from immune tolerance to inflammation. We also evaluate therapeutic DC reprogramming strategies and their potential implications for targeted immunometabolic intervention in diabetes.

Endoplasmic reticulum stress in Hashimoto’s thyroiditis: a candidate amplification node linking thyroid-specific vulnerability and immune dysregulation

A testable positive-feedback perspective in which thyrocyte ERS injury and immune effector amplification may mutually reinforce one another is proposed, in which thyrocyte ERS injury and immune effector amplification may mutually reinforce one another.