Publications by authors named "Spits H"

Background: Antigen-specific memory B cells play a key role in the induction of desensitization and remission to food allergens in oral immunotherapy and in the development of natural tolerance (NT). Here, we characterized milk allergen Bos d 9-specific B cells in oral allergen-specific immunotherapy (OIT) and in children spontaneously outgrowing cow's milk allergy (CMA) due to NT.

Methods: Samples from children with CMA who received oral OIT (before, during, and after), children who naturally outgrew CMA (NT), and healthy individuals were received from Stanford biobank.

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Article Synopsis
  • - ILC2s are important for type 2 immunity and play a role in chronic inflammatory conditions like asthma.
  • - Research shows that resting ILC2s in humans retain a marker (CD45RO) associated with activated inflammatory ILC2s, while also decreasing another typical marker (CD127) in specific tissues.
  • - When isolated and stimulated, these CD127-CD45RO+ ILC2s demonstrate enhanced growth and cytokine production, suggesting that human ILC2s can develop an innate immune memory, prompting a reevaluation of how these cells are identified.
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Background: The immunogenic nature of metastatic colorectal cancer (CRC) with high microsatellite instability (MSI-H) underlies their responsiveness to immune checkpoint blockade (ICB). However, resistance to ICB is commonly observed, and is associated with the presence of peritoneal-metastases and ascites formation. The mechanisms underlying this site-specific benefit of ICB are unknown.

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The family of innate lymphoid cells (ILCs) are composed of five canonical subsets, NK cells, ILC1, ILC2, ILC3 and Lymphoid tissue inducer cells. ILCs have important functions in early stages of immune response towards infectious agents. ILCs are highly plastic enabling rapid modification of their functions dependent on the type of microbe and tissue environment to optimally counter these microbes.

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Innate lymphoid cells (ILC) are important barrier tissue immune regulators. They play a pivotal role in early non-specific protection against infiltrating pathogens, regulation of epithelial integrity, suppression of pro-inflammatory immune responses and shaping the intestinal microbiota. GATA2 haploinsufficiency causes an immune disorder that is characterized by bone marrow failure and (near) absence of monocytes, dendritic cells, B cells and natural killer (NK) cells.

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The chapters of this book give a comprehensive overview of the current state of knowledge of ILCs. Most of this knowledge stems from studies in mouse models. Translation to the human situation is not always straightforward because of differences between human and mouse ILCs and the microenvironments in which these ILCs are operating.

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Article Synopsis
  • Innate lymphoid cells (ILCs) are flexible immune cells residing mainly in mucosal tissues, playing a role in maintaining balance and responding to inflammation based on environmental signals.
  • The study found two subsets of ILCs in tonsils, where CD45RA ILCs displayed low activity (quiescence) while CD62L ILCs exhibited similarities to naïve ILCs without fully differentiating traits.
  • Differentiation of CD62L ILCs leads to metabolic changes necessary for their immune functions, particularly in inflamed tissues like those in inflammatory bowel disease, indicating potential therapeutic targets to restore immune balance.
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More than a decade ago, type 2 innate lymphoid cells (ILC2s) were discovered to be members of a family of innate immune cells consisting of five subsets that form a first line of defence against infections before the recruitment of adaptive immune cells. Initially, ILC2s were implicated in the early immune response to parasitic infections, but it is now clear that ILC2s are highly diverse and have crucial roles in the regulation of tissue homeostasis and repair. ILC2s can also regulate the functions of other type 2 immune cells, including T helper 2 cells, type 2 macrophages and eosinophils.

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Monoclonal antibodies targeting immune checkpoints improved clinical outcome of patients with malignant melanoma. However, the mechanisms are not fully elucidated. Since immune check-point receptors are also expressed by helper innate lymphoid cells (ILCs), we investigated the capability of immune checkpoints inhibitors to modulate ILCs in metastatic melanoma patients as well as melanoma cells effects on ILC functions.

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Phenotypic definition of helper ILC1 and NK cells is problematic due to overlapping markers. Recently we showed the identification of cytotoxic ILC3s characterized by expression of CD94. Here we analyse CD127+ ILCs and NK cells in intestinal lamina propria from healthy donors and Crohn's disease patients and identify two populations of CD127+CD94+ ILCs, designated population A and B, that can be distinguished on the expression of CD117, CD18 and cytotoxic molecules.

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Stromal-derived follicular dendritic cells (FDCs) are essential for germinal centers (GCs), the site where B cells maturate their antibodies. FDCs present native antigen to B cells and maintain a CXCL13 gradient to form the B cell follicle. Yet despite their essential role, the transcriptome of human FDCs remains undefined.

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Food allergy is an increasingly prevalent disease driven by uncontrolled type 2 immune response. Currently, knowledge about the underlying mechanisms that initiate and promote the immune response to dietary allergens is limited. Patients with food allergy are commonly sensitized through the skin in their early life, later on developing allergy symptoms within the gastrointestinal tract.

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Group 2 innate lymphoid cells (ILC2s) orchestrate protective type 2 immunity and have been implicated in various immune disorders. In the mouse, circulatory inflammatory ILC2s (iILC2s) were identified as a major source of type 2 cytokines. The human equivalent of the iILC2 subset remains unknown.

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The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10 ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1 but not KLRG1 ILC2 produced IL-10 upon activation with IL-33 and retinoic acid.

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Pneumonia represents a major health care burden and Gram-negative bacteria provide an increasing therapeutic challenge at least in part through the emergence of multidrug-resistant strains. IL-33 is a multifunctional cytokine belonging to the IL-1 family that can affect many different cell types. We sought here to determine the effect of recombinant IL-33 on the host response during murine pneumonia caused by the common Gram-negative pathogen Klebsiella pneumoniae.

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Human ILCs are classically categorized into five subsets; cytotoxic CD127 CD94 NK cells and non-cytotoxic CD127 CD94 , ILC1s, ILC2s, ILC3s, and LTi cells. Here, we identify a previously unrecognized subset within the CD127 ILC population, characterized by the expression of the cytotoxic marker CD94. These CD94 ILCs resemble conventional ILC3s in terms of phenotype, transcriptome, and cytokine production, but are highly cytotoxic.

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Targeted cancer therapy with monoclonal antibodies has proven successful for different cancer types but is limited by the availability of suitable antibody targets. CD43s, a unique sialylated form of CD43 expressed by hematologic malignancies, is a recently identified target and antibodies interacting with CD43s may have therapeutic potential against acute myeloid leukemia (AML) and myelodysplastic syndrome. CD43s is recognized by the human antibody AT1413, that was derived from a high-risk AML patient who successfully cleared leukemia after allogeneic stem cell transplantation.

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Autoreactive B cells mediate autoimmune pathology, but exactly how remains unknown. A hallmark of rheumatoid arthritis (RA), a common autoimmune disease, is the presence of disease-specific anticitrullinated protein antibodies (ACPAs). Here, we showed that ACPA-positive B cells in patients with RA strongly expressed T cell-stimulating ligands, produced abundant proinflammatory cytokines, and were proliferative while escaping inhibitory signals.

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Five subsets of ILCs are extensively described, Lymphoid Tissue inducer (LTi) cells, cytotoxic NK cells and non-cytotoxic helper ILC1s, ILC2s and ILC3s. So far, the main focus has been on the potent cytokine production by helper ILCs and their plastic nature that allows them to switch function and phenotype upon environmental changes. Recent advances in the field indicate the presence of cytotoxic helper ILCs that are distinct from conventional NK cells.

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