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Article ; Online: Neutrophil-T cell crosstalk in inflammatory bowel disease.

Kvedaraite, Egle

2021 Volume 164, Issue 4, Page(s) 657–664

Abstract: Neutrophils are the most abundant leucocytes in human blood, promptly recruited to the site of tissue injury, where they orchestrate inflammation and tissue repair. The multifaceted functions of neutrophils have been more appreciated during the recent ... ...

Abstract	Neutrophils are the most abundant leucocytes in human blood, promptly recruited to the site of tissue injury, where they orchestrate inflammation and tissue repair. The multifaceted functions of neutrophils have been more appreciated during the recent decade, and these cells are now recognized as sophisticated and essential players in infection, cancer and chronic inflammatory diseases. Consequently, our understanding of the role of neutrophils in inflammatory bowel disease (IBD), their immune responses and their ability to shape adaptive immunity in the gut have been recognized. Here, current knowledge on neutrophil responses in IBD and their capacity to influence T cells are summarized with an emphasis on the role of these cells in human disease.
MeSH term(s)	Animals ; Antigen Presentation ; Biomarkers ; Cell Communication/genetics ; Cell Communication/immunology ; Cytokines/metabolism ; Disease Susceptibility/immunology ; Genetic Predisposition to Disease ; Humans ; Inflammation Mediators/metabolism ; Inflammatory Bowel Diseases/etiology ; Inflammatory Bowel Diseases/metabolism ; Inflammatory Bowel Diseases/pathology ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Neutrophils/immunology ; Neutrophils/metabolism ; Neutrophils/pathology ; Signal Transduction ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; T-Lymphocytes/pathology
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators
Language	English
Publishing date	2021-07-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13391
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Article ; Online: Human dendritic cells in cancer.

Kvedaraite, Egle / Ginhoux, Florent

Science immunology

2022 Volume 7, Issue 70, Page(s) eabm9409

Abstract: Dendritic cells (DCs) are professional antigen-presenting cells, orchestrating innate and adaptive immunity during infections, autoimmune diseases, and malignancies. Since the discovery of DCs almost 50 years ago, our understanding of their biology in ... ...

Abstract	Dendritic cells (DCs) are professional antigen-presenting cells, orchestrating innate and adaptive immunity during infections, autoimmune diseases, and malignancies. Since the discovery of DCs almost 50 years ago, our understanding of their biology in humans has increased substantially. Here, we review both antitumor and tolerogenic DC responses in cancer and discuss lineage-specific contributions by their functionally specialized subsets, including the conventional DC (cDC) subsets cDC1 and cDC2, the newly described DC3, and the plasmacytoid DCs (pDCs), focusing on the human setting. In addition, we review the lineage-unrestricted "mature DCs enriched in immunoregulatory molecules" (mregDC) state recently described across different human tumors.
MeSH term(s)	Adaptive Immunity ; Dendritic Cells ; Humans ; Neoplasms
Language	English
Publishing date	2022-04-01
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ISSN	2470-9468
ISSN (online)	2470-9468
DOI	10.1126/sciimmunol.abm9409
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Article: Plasma Signaling Factors in Patients With Langerhans Cell Histiocytosis (LCH) Correlate With Relative Frequencies of LCH Cells and T Cells Within Lesions.

Mitchell, Jenée / Kvedaraite, Egle / von Bahr Greenwood, Tatiana / Lourda, Magda / Henter, Jan-Inge / Berzins, Stuart P / Kannourakis, George

Frontiers in pediatrics

2022 Volume 10, Page(s) 872859

Abstract: Langerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the ... ...

Abstract	Langerhans cell histiocytosis (LCH) lesions contain an inflammatory infiltrate of immune cells including myeloid-derived LCH cells. Cell-signaling proteins within the lesion environment suggest that LCH cells and T cells contribute majorly to the inflammation. Foxp3+ regulatory T cells (Tregs) are enriched in lesions and blood from patients with LCH and are likely involved in LCH pathogenesis. In contrast, mucosal associated invariant T (MAIT) cells are reduced in blood from these patients and the consequence of this is unknown. Serum/plasma levels of cytokines have been associated with LCH disease extent and may play a role in the recruitment of cells to lesions. We investigated whether plasma signaling factors differed between patients with active and non-active LCH. Cell-signaling factors (38 analytes total) were measured in patient plasma and cell populations from matched lesions and/or peripheral blood were enumerated. This study aimed at understanding whether plasma factors corresponded with LCH cells and/or LCH-associated T cell subsets in patients with LCH. We identified several associations between plasma factors and lesional/circulating immune cell populations, thus highlighting new factors as potentially important in LCH pathogenesis. This study highlights plasma cell-signaling factors that are associated with LCH cells, MAIT cells or Tregs in patients, thus they are potentially important in LCH pathogenesis. Further study into these associations is needed to determine whether these factors may become suitable prognostic indicators or therapeutic targets to benefit patients.
Language	English
Publishing date	2022-06-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2022.872859
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Article ; Online: Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma.

Sveijer, Malin / von Bahr Greenwood, Tatiana / Jädersten, Martin / Kvedaraite, Egle / Zetterberg, Henrik / Blennow, Kaj / Lourda, Magda / Gavhed, Désirée / Henter, Jan-Inge

British journal of haematology

2022 Volume 198, Issue 4, Page(s) 721–728

Abstract: Patients with Langerhans cell histiocytosis (LCH) may develop progressive neurodegeneration in the central nervous system (ND-CNS-LCH). Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) is a promising biomarker to detect and monitor ND-CNS- ... ...

Abstract	Patients with Langerhans cell histiocytosis (LCH) may develop progressive neurodegeneration in the central nervous system (ND-CNS-LCH). Neurofilament light protein (NFL) in cerebrospinal fluid (CSF) is a promising biomarker to detect and monitor ND-CNS-LCH. We compared paired samples of NFL in plasma (p-NFL) and CSF in 10 patients (19 samples). Nine samples had abnormal CSF-NFL (defined as ≥380 ng/l) with corresponding p-NFL ≥ 2 ng/l. Ten samples had CSF-NFL < 380 ng/l; eight (80%) with p-NFL < 2 ng/l (p < 0.001; Fisher's exact test). Thus, our results suggest that p-NFL may be used to screen for ND-CNS-LCH. Further studies are encouraged, including the role of p-NFL for monitoring of ND-CNS-LCH.
MeSH term(s)	Biomarkers ; Cognitive Dysfunction ; Histiocytosis, Langerhans-Cell/diagnosis ; Humans ; Intermediate Filaments ; Neurofilament Proteins/cerebrospinal fluid
Chemical Substances	Biomarkers ; Neurofilament Proteins
Language	English
Publishing date	2022-05-17
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.18247
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Article ; Online: Myeloid cells from Langerhans cell histiocytosis patients exhibit increased vesicle trafficking and an altered secretome capable of activating NK cells.

Hagey, Daniel W / Kvedaraite, Egle / Akber, Mira / Görgens, André / Javadi, Joman / Von Bahr Greenwood, Tatiana / Björklund, Caroline / Åkefeldt, Selma Olsson / Hannegård-Hamrin, Tova / Arnell, Henrik / Dobra, Katalin / Herold, Nikolas / Svensson, Mattias / El Andaloussi, Samir / Henter, Jan-Inge / Lourda, Magda

Haematologica

2023 Volume 108, Issue 9, Page(s) 2422–2434

Abstract: Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations ... ...

Abstract	Langerhans cell histiocytosis (LCH) is a potentially life-threatening inflammatory myeloid neoplasia linked to pediatric neurodegeneration, whereby transformed LCH cells form agglomerated lesions in various organs. Although MAP-kinase pathway mutations have been identified in LCH cells, the functional consequences of these mutations and the mechanisms that cause the pathogenic behavior of LCH cells are not well understood. In our study, we used an in vitro differentiation system and RNA-sequencing to compare monocyte-derived dendritic cells from LCH patients to those derived from healthy controls or patients with Crohn's disease, a non-histiocytic inflammatory disease. We observed that interferon-γ treatment exacerbated intrinsic differences between LCH patient and control cells, including strikingly increased endo- and exocytosis gene activity in LCH patients. We validated these transcriptional patterns in lesions and functionally confirmed that LCH cells exhibited increased endo- and exocytosis. Furthermore, RNA-sequencing of extracellular vesicles revealed the enrichment of pathological transcripts involved in cell adhesion, MAP-kinase pathway, vesicle trafficking and T-cell activation in LCH patients. Thus, we tested the effect of the LCH secretome on lymphocyte activity and found significant activation of NK cells. These findings implicate extracellular vesicles in the pathology of LCH for the first time, in line with their established roles in the formation of various other tumor niches. Thus, we describe novel traits of LCH patient cells and suggest a pathogenic mechanism of potential therapeutic and diagnostic importance.
MeSH term(s)	Humans ; Child ; Secretome ; Histiocytosis, Langerhans-Cell/genetics ; Histiocytosis, Langerhans-Cell/drug therapy ; Histiocytosis, Langerhans-Cell/pathology ; Myeloid Cells/metabolism ; Killer Cells, Natural/metabolism ; Neoplasms
Language	English
Publishing date	2023-09-01
Publishing country	Italy
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2022.282638
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Article ; Online: Foxp3

Mitchell, Jenée / Kelly, Jason / Kvedaraite, Egle / von Bahr Greenwood, Tatiana / Henter, Jan-Inge / Pellicci, Daniel G / Berzins, Stuart P / Kannourakis, George

Clinical immunology (Orlando, Fla.)

2020 Volume 215, Page(s) 108418

Abstract: Langerhans cell histiocytosis (LCH) lesions contain myeloid lineage 'LCH' cells. Regulatory T cells (Tregs) are also enriched within lesions, although their role in LCH pathogenesis is unknown. LCH cells are thought to produce the transforming growth ... ...

Abstract	Langerhans cell histiocytosis (LCH) lesions contain myeloid lineage 'LCH' cells. Regulatory T cells (Tregs) are also enriched within lesions, although their role in LCH pathogenesis is unknown. LCH cells are thought to produce the transforming growth factor beta (TGF-β) within lesions, however whether Tregs contribute is unestablished. Using flow cytometry, we analyzed relative frequencies of live Tregs from LCH patients and identified CD56 expression and TGF-β production by lesion Tregs. While CD56
MeSH term(s)	Adolescent ; Adult ; Aged ; CD56 Antigen/immunology ; CD8-Positive T-Lymphocytes/immunology ; Child ; Child, Preschool ; Female ; Forkhead Transcription Factors/immunology ; Histiocytosis, Langerhans-Cell/immunology ; Humans ; Infant ; Inflammation/immunology ; Langerhans Cells/immunology ; Male ; Middle Aged ; T-Lymphocytes, Regulatory/immunology ; Transforming Growth Factor beta/immunology
Chemical Substances	CD56 Antigen ; FOXP3 protein, human ; Forkhead Transcription Factors ; NCAM1 protein, human ; Transforming Growth Factor beta
Language	English
Publishing date	2020-04-10
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1459903-x
ISSN	1521-7035 ; 1521-6616
ISSN (online)	1521-7035
ISSN	1521-6616
DOI	10.1016/j.clim.2020.108418
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Article ; Online: The single-cell transcriptional landscape of innate and adaptive lymphocytes in pediatric-onset colitis.

Kokkinou, Efthymia / Soini, Tea / Pandey, Ram Vinay / van Acker, Aline / Theorell, Jakob / Czarnewski, Paulo / Kvedaraite, Egle / Vandamme, Niels / Lourda, Magda / Sorini, Chiara / Weigel, Whitney / Carrasco, Anna / Tibbitt, Christopher Andrew / Schlums, Heinrich / Lindforss, Ulrik / Nordenvall, Caroline / Ljunggren, Malin / Ideström, Maja / Svensson, Mattias /

Henter, Jan-Inge / Villablanca, Eduardo J / Bryceson, Yenan T / Rolandsdotter, Helena / Mjösberg, Jenny

Cell reports. Medicine

2023 Volume 4, Issue 5, Page(s) 101038

Abstract: 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 ... ...

Abstract	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 of naive-like CD45RA
MeSH term(s)	Humans ; Child ; Lymphocytes ; Immunity, Innate/genetics ; Colitis/genetics ; Inflammatory Bowel Diseases ; T-Lymphocytes
Language	English
Publishing date	2023-05-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2666-3791
ISSN (online)	2666-3791
DOI	10.1016/j.xcrm.2023.101038
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Article ; Online: Type I Interferon Autoantibodies Correlate With Cellular Immune Alterations in Severe COVID-19.

Strunz, Benedikt / Maucourant, Christopher / Mehta, Adi / Wan, Hui / Du, Likun / Sun, Dan / Chen, Puran / Nordlander, Anna / Gao, Yu / Cornillet, Martin / Bister, Jonna / Kvedaraite, Egle / Christ, Wanda / Klingström, Jonas / Geanon, Daniel / Parke, Åsa / Ekwall-Larson, Anna / Rivino, Laura / MacAry, Paul A /

Aleman, Soo / Buggert, Marcus / Ljunggren, Hans-Gustaf / Pan-Hammarström, Qiang / Lund-Johansen, Fridtjof / Strålin, Kristoffer / Björkström, Niklas K

The Journal of infectious diseases

2024

Abstract: Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is ... ...

Abstract	Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). Methods: This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. Results: aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. Conclusions: Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.
Language	English
Publishing date	2024-02-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jiae036
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Article ; Online: High prevalence of peripheral lymphopenia in Langerhans cell histiocytosis.

Lourda, Magda / Widesköld, Sofie / Kvedaraite, Egle / Gavhed, Désirée / Akber, Mira / von Bahr Greenwood, Tatiana / Svensson, Mattias / Olsson-Åkefeldt, Selma / Henter, Jan-Inge

British journal of haematology

2020 Volume 191, Issue 1, Page(s) 115–119

MeSH term(s)	Adolescent ; Child ; Child, Preschool ; Female ; Histiocytosis, Langerhans-Cell/complications ; Histiocytosis, Langerhans-Cell/epidemiology ; Humans ; Infant ; Lymphopenia/epidemiology ; Lymphopenia/etiology ; Male ; Prevalence ; Retrospective Studies
Language	English
Publishing date	2020-07-08
Publishing country	England
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	80077-6
ISSN	1365-2141 ; 0007-1048
ISSN (online)	1365-2141
ISSN	0007-1048
DOI	10.1111/bjh.16923
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Article ; Online: Altered Populations of Unconventional T Cell Lineages in Patients with Langerhans Cell Histiocytosis.

Mitchell, Jenée / Kvedaraite, Egle / von Bahr Greenwood, Tatiana / Henter, Jan-Inge / Pellicci, Daniel G / Berzins, Stuart P / Kannourakis, George

Scientific reports

2018 Volume 8, Issue 1, Page(s) 16506

Abstract: Langerhans cell histiocytosis (LCH) lesions are defined by the presence of ... ...

Abstract	Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a
MeSH term(s)	Adolescent ; Adult ; Aged ; Cell Lineage/immunology ; Child ; Child, Preschool ; Cytokines/metabolism ; Female ; Histiocytosis, Langerhans-Cell/blood ; Histiocytosis, Langerhans-Cell/epidemiology ; Histiocytosis, Langerhans-Cell/immunology ; Humans ; Infant ; Lymphocyte Count ; Male ; Middle Aged ; Phenotype ; Population Surveillance ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism ; T-Lymphocytes/immunology ; T-Lymphocytes/metabolism ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Young Adult
Chemical Substances	Cytokines
Language	English
Publishing date	2018-11-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-018-34873-y
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