Chiara Sorini

Karolinska Institutet | KI · Department of Clinical Neuroscience

The gut environment modulates the pathogenesis of type 1 diabetes (T1D), but how it affects autoimmunity toward pancreatic β-cells, a self-tissue located outside the intestine, is still unclear. In the small intestine, lamina propria dendritic cells (LPDCs) induce peripheral differentiation of FoxP3(+) regulatory T (Treg) cells. We tested the hypot...

Significance Functional loss of gut barrier integrity with subsequent increased antigen trafficking and occurrence of low-grade intestinal inflammation precede the onset of type 1 diabetes (T1D) in patients and preclinical models, thus suggesting that these events are mechanistically linked to the autoimmune pathogenesis of the disease. However, a...

In this issue of Immunity, Wang et al. report that the recognition of lysophosphatidyl serine via the receptor GPR43 confers type 3 innate lymphoid cells with the capacity to sense damage-induced cell death, which in turn triggers interleukin-22-dependent tissue repair.

Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. To deeply characterize the host-microbiota environment in H. pylori-infected (HPI) stomachs, we collected human gastric tissues and performed metagenomic sequencing, single-cell RNA-Seq (scRNA-Seq), flow cytometry, and fluorescent microscopy. HP...

Uncontrolled regeneration leads to neoplastic transformation1, 2–3. The intestinal epithelium requires precise regulation during continuous homeostatic and damage-induced tissue renewal to prevent neoplastic transformation, suggesting that pathways unlinking tumour growth from regenerative processes must exist. Here, by mining RNA-sequencing datase...

Stromal cells support epithelial cell and immune cell homeostasis and play an important role in inflammatory bowel disease (IBD) pathogenesis. Here, we quantify the stromal response to inflammation in pediatric IBD and reveal subset-specific inflammatory responses across colon segments and intestinal layers. Using data from a murine dynamic gut inj...

Innate lymphoid cells (ILCs) are considered innate counterparts of adaptive T cells; however, their common and unique transcriptional signatures in pediatric inflammatory bowel disease (pIBD) are largely unknown. Here, we report a dysregulated colonic ILC composition in pIBD colitis that correlates with inflammatory activity, including accumulation...

Therapeutic promotion of intestinal regeneration holds great promise, but defining the cellular mechanisms that influence tissue regeneration remains an unmet challenge. To gain insight into the process of mucosal healing, we longitudinally examined the immune cell composition during intestinal damage and regeneration. B cells were the dominant cel...

Mast cell accumulation is a hallmark of a number of diseases including allergic asthma and systemic mastocytosis. IgE-mediated crosslinking of the FceRI receptors causes mast cell activation and contributes to disease pathogenesis. The mast cell lineage is one of the least studied among the hematopoietic cell lineages and there are still controvers...

Objective. Helicobacter pylori colonization of the gastric niche can persist for years in asymptomatic individuals. Although latent H. pylori infection can progress to cancer, a detailed survey of the microbiome and immune composition in the chronically infected stomach is still lacking. Design. We collected human gastric tissues and performed meta...

Dendritic cells (DCs) patrol tissues and transport antigens to lymph nodes to initiate adaptive immune responses. Within tissues, DCs constitute a complex cell population composed of distinct subsets that can exhibit different activation states and functions. How tissue-specific cues orchestrate DC diversification remains elusive. Here, we show tha...

The intestinal epithelium is continuously exposed to deleterious environmental factors which might cause aberrant immune responses leading to inflammatory disorders. However, what environmental factors might contribute to disease are yet poorly understood. Here, to overcome the lack of in vivo models suitable for screening of environmental factors...

Mast cell accumulation is a hallmark of a number of diseases including allergic asthma and systemic mastocytosis. IgE-mediated crosslinking of the FcεRI receptors causes mast cell activation and contributes to disease pathogenesis. The mast cell lineage is one of the least studied among the hematopoietic cell lineages and there are still controvers...

The study of human macrophages and their ontogeny is an important unresolved issue. Here, we use a humanized mouse model expressing human cytokines to dissect the development of lung macrophages from human hematopoiesis in vivo. Human CD34⁺ hematopoietic stem and progenitor cells (HSPCs) generated three macrophage populations, occupying separate an...

Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from ∼1,000 single-so...

The intestinal barrier provides the host with a strong defense line against the external environment playing also a pivotal role in the crosstalk between the gut microbiota and the immune system. Notably, increasing lines of evidence concerning autoimmune disorders such as Multiple Sclerosis (MS) report an imbalance in both intestinal microbiota co...

Clinical manifestations and response to therapies in ulcerative colitis (UC) are heterogeneous, yet patient classification criteria for tailored therapies are currently lacking. Here, we present an unsupervised molecular classification of UC patients, concordant with response to therapy in independent retrospective cohorts. We show that classical c...

Interleukin (IL)‐10 plays key role in controlling intestinal inflammation. IL‐10‐deficient mice and patients with mutations in IL‐10 or its receptor, IL‐10R, show increased susceptibility to inflammatory bowel diseases (IBD). Protein tyrosine phosphatase PTPN22 controls immune cell activation and the equilibrium between regulatory and effector T ce...

Recent evidence suggests that the intestinal environment and, specifically, modifications of the microbiome profile, regulate the pathogenesis of extra-intestinal autoimmune diseases such as Type 1 Diabetes (T1D) by inducing intestinal inflammation and increasing gut permeability. Although low-grade intestinal inflammation and alterations of gut ba...

Background Although ulcerative colitis (UC) patients show heterogeneous clinical manifestation, such as diverse response to biological therapies, they are classified as one group. Therefore, an unsupervised molecular re-classification of UC patients has been evoked to design tailored therapies. Moreover, independently on the re-classification, thos...

Abstrasct Despite the fact that ulcerative colitis (UC) patients show heterogeneous clinical manifestation and diverse response to biological therapies, all UC patients are classified as one group. Therefore, there is a lack of tailored therapies. In order to design these, an unsupervised molecular re-classification of UC patients is evoked. Classi...

IL-10 is a prototypical anti-inflammatory cytokine, which is fundamental to the maintenance of immune homeostasis, especially in the intestine. There is an assumption that cells producing IL-10 have an immunoregulatory function. However, here we report that IL-10-producing CD4⁺ T cells are phenotypically and functionally heterogeneous. By combining...

Over the course of evolution, mammalian body surfaces have adapted their complex immune system to allow a harmless coexistence with the commensal microbiota. The adaptive immune response, in particular CD4⁺ T cell-mediated, is crucial to maintain intestinal immune homeostasis by discriminating between harmless (e.g., dietary compounds and intestina...

iNKT cells play different immune function depending on their cytokine-secretion phenotype. iNKT17 cells predominantly secrete IL-17 and have an effector and pathogenic role in the pathogenesis of autoimmune diseases such as type 1 diabetes (T1D). In line with this notion, non-obese diabetic (NOD) mice that spontaneously develop T1D have an increase...

Cellular and Molecular Immunology aims to report the dynamic progress being made in China and abroad in immunological research, and welcomes high-quality Research Articles, Reviews and Brief Reports across a broad range of topics including, but not limited to, clinical immunology, comparative immunology, immunobiology, immunogenetics, immunological...

T helper 17 (T H 17) cells are key players in multiple sclerosis (MS), and studies in animal models demonstrated that effector T H 17 cells that trigger brain autoimmunity originate in the intestine. We validate in humans the crucial role of the intestinal environment in promoting T H 17 cell expansion in MS patients. We found that increased freque...

NKT17 cells represent a functional subset of Vα14 invariant NKT (iNKT) cells with important effector functions in infections and autoimmune diseases. The mechanisms that drive NKT17 cell differentiation in the thymus are still largely unknown. The percentage of NKT17 cells has a high variability between murine strains due to differential thymic dif...

The Supplementary Material contains two Figures that illustrate the gating strategies for identification of dendritic cell and T cell subsets in different organs (intestinal mucosa, pancreatic lymph nodes and pancreatic islets).

The gut microbiota modulates the autoimmune pathogenesis of type 1 diabetes (T1D) via mechanisms that remain largely unknown. The inflammasome components are innate immune sensors that are highly influenced by the gut environment and play pivotal roles in maintaining intestinal immune homeostasis. In this study we show that modifications of the gut...

The pathogenesis of organ-specific autoimmune diseases such as Type 1 Diabetes (T1D) is regulated by genetic and environmental factors. There is increasing evidence that environmental factors acting at the intestinal level, with a special regard to the diverse bacterial species that constitute the microbiota, influence the course of autoimmune dise...

Invariant natural killer T (iNKT) cells represent an important regulatory T-cell subset that perceives signals of danger and/or cellular distress and modulate the adaptive immune response accordingly. In the presence of pathogens, iNKT cells acquire an adjuvant function that is fundamental to boost anti-microbial and anti-tumor immunity. At the sam...

Environmental factors that act at the intestinal level such as diet, drugs, and microflora have a high impact on the pathogenesis of autoimmune Type 1 Diabetes (T1D), but it is still unclear how the gut milieu affects autoimmunity outside the intestine. Here we show that peripheral FoxP3+ Treg cell differentiation, a mechanism that takes place in t...