<scp>CD</scp>300a expression is modulated in atopic dermatitis and could influence the inflammatory response

Karra, Laila; Gangwar, Roopesh Singh; Puzzovio, Pier Giorgio; Fyhrquist, Nanna; Minai-Fleminger, Yael; Landolina, Nadine; Simon, Hans‐Uwe; Alenius, Harri; Leibovici, Vera; Simon, Dagmar; Levi‐Schaffer, Francesca

doi:10.1111/all.13724

Cited by 16 publications

(29 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The results clearly show that there are several DMRs associated with food sensitization that are biologically plausible to predispose those children to react to food allergens in contrast with children that are only sensitized to airborne allergens. This study revealed for the first time that DNA methylation levels in CD300A were lower in IgE-sensitized children either to airborne allergens (Table 2) or to both, airborne plus food allergen sensitization (Table 4), supporting previous studies suggesting regulatory functions of this receptor on atopy and IgE-mediated, allergic inflammation [25][26][27]. Our results may also help to understand the biology of why some individuals are naturally predisposed to become IgE polysensitized.…”

Section: Discussionsupporting

confidence: 86%

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

Acevedo

Scala²,

Merid

et al. 2021

IJMS

View full text Add to dashboard Cite

DNA methylation changes may predispose becoming IgE-sensitized to allergens. We analyzed whether DNA methylation in peripheral blood mononuclear cells (PBMC) is associated with IgE sensitization at 5 years of age (5Y). DNA methylation was measured in 288 PBMC samples from 74 mother/child pairs from the birth cohort ALADDIN (Assessment of Lifestyle and Allergic Disease During INfancy) using the HumanMethylation450BeadChip (Illumina). PBMCs were obtained from the mothers during pregnancy and from their children in cord blood, at 2 years and 5Y. DNA methylation levels at each time point were compared between children with and without IgE sensitization to allergens at 5Y. For replication, CpG sites associated with IgE sensitization in ALADDIN were evaluated in whole blood DNA of 256 children, 4 years old, from the BAMSE (Swedish abbreviation for Children, Allergy, Milieu, Stockholm, Epidemiology) cohort. We found 34 differentially methylated regions (DMRs) associated with IgE sensitization to airborne allergens and 38 DMRs associated with sensitization to food allergens in children at 5Y (Sidak p ≤ 0.05). Genes associated with airborne sensitization were enriched in the pathway of endocytosis, while genes associated with food sensitization were enriched in focal adhesion, the bacterial invasion of epithelial cells, and leukocyte migration. Furthermore, 25 DMRs in maternal PBMCs were associated with IgE sensitization to airborne allergens in their children at 5Y, which were functionally annotated to the mTOR (mammalian Target of Rapamycin) signaling pathway. This study supports that DNA methylation is associated with IgE sensitization early in life and revealed new candidate genes for atopy. Moreover, our study provides evidence that maternal DNA methylation levels are associated with IgE sensitization in the child supporting early in utero effects on atopy predisposition.

show abstract

Section: Discussionsupporting

confidence: 86%

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

Acevedo

Scala²,

Merid

et al. 2021

IJMS

View full text Add to dashboard Cite

show abstract

“…Significant levels of IL-17A, both at mRNA and protein levels were found in asthma patients (32). IL-17A was detected in the skin of OVA/SEB-induced AD mice (31). Correspondingly with the aforementioned evidence, our AP model showed significantly elevated levels of IL-4 simultaneously with a trend of increased levels of both IL-17A and INFg.…”

Section: Discussionsupporting

confidence: 76%

“…Many allergic diseases are characterized by the involvement of a mixed Th2 and Th1 (28)(29)(30)(31) response and, as demonstrated by more recent evidence, of a Th17 one (32). For example, an AD murine model induced by OVA/SEB displayed increased mRNA levels of the Th2 cytokines IL-4 and IL-13, together with the Th1-related cytokines INFg and 12p40 (12).…”

Section: Discussionmentioning

confidence: 99%

A novel mast cell-dependent allergic peritonitis model

Pahima

Puzzovio

Levi‐Schaffer

2021

Preprint

Self Cite

View full text Add to dashboard Cite

Background: Typical murine models of allergic inflammation are induced by the combination of ovalbumin and aluminum hydroxide. However, accumulating evidence indicates that, in models of asthma and atopic dermatitis, allergic inflammation can be generated in the absence of aluminum hydroxide. Moreover, co-administration of S. aureus enterotoxin B with ovalbumin can enhance inflammation. Objective: The objective of this study was to establish a rapid and mast cell-dependent murine model of allergic inflammation by inducing allergic peritonitis using ovalbumin and S. aureus enterotoxin B. Methods: Allergic peritonitis was induced in C57BL/6 mice by subcutaneous sensitization and intraperitoneal challenge with ovalbumin and S. aureus enterotoxin B. Disease characteristics were assessed by flow cytometry, ELISA, Trypan Blue exclusion and colorimetric assays. Results: Time course of the allergic peritonitis revealed a peak of peritoneal inflammation 48h after challenge, as assessed by total cells and eosinophil counts. Decrease of cell numbers started 96h post challenge with complete clearance within 168h. Moreover, significantly higher levels of tryptase and increased vascular permeability were found 30 min following challenge. Allergic inflammation induction by ovalbumin and S. aureus enterotoxin B was impaired in mast cells deficient mice and partially restored by mice reconstitution with bone marrow derived mast cells, indicating the mast cell role in this model. Conclusion: We present a novel model of allergic peritonitis that is mast cell-dependent, simple and robust. Moreover, the use of S. aureus enterotoxin B better resembles human allergic inflammation, which is known to be characterized by the colonization of Staphylococcus aureus.

show abstract

“…Interaction of CD300a with phosphatidylserine and phosphatidylethanolamine present in Dengue virus enhance its internalization, favoring infection . Recently, up‐regulated CD300a expression has been reported in atopic dermatitis lesional skin and CD300a KO mice presented increased lesions in atopic dermatitis when compared to WT mice …”

Section: Discussionmentioning

confidence: 99%

The immunoreceptor CD300a controls the intensity of inflammation and dysfunction in a model of Ag-induced arthritis in mice

Valiate

Alvarez

Karra

et al. 2019

Journal of Leukocyte Biology

Self Cite

View full text Add to dashboard Cite

CD300a is an inhibitory immunoreceptor expressed in lymphoid and myeloid cells. This study evaluates whether CD300a plays a role in the control of joint inflammation in a model of Aginduced arthritis (AIA) in mice. CD300a was found to be expressed mostly on neutrophils and its expression was enhanced on neutrophils that migrated to the inflamed synovial cavity. Joint inflammation, as characterized by neutrophil accumulation, was significantly greater in CD300a KO (CD300a −/− ) mice subjected to AIA, as compared to WT mice. This was associated with joint dysfunction, as measured by lower mechanical nociception threshold. There was greater production of the chemokine CXCL1 and the cytokine IL-6 in joints of CD300a −/− mice. In vitro, M s from CD300a −/− mice released higher concentrations of CXCL1 and IL-6 in response to LPS. Splenocytes from immunized CD300a −/− mice produced increased levels of IFN-and IL-17 and lower levels of IL-10 when challenged with Ag than cells from WT mice. Neutrophils lacking the CD300a gene had greater chemotactic activity in response to fMLP, CXCL1, and LTB4 than WT neutrophils.In conclusion, these results reveal that the absence of CD300a promotes exacerbation of inflammation in a model of Ag-induced arthritis, suggesting that CD300a is an important receptor for negatively controlling the inflammatory response in this model. Mechanistically, CD300a seems to regulate the activity of various immune cells types involved in the process, including neutrophils, M s, and lymphocytes. K E Y W O R D S joint inflammation, neutrophils, pain, cytokines, CD300a, inflammation, arthritis, regulation, mice of the ITIM are phosphorylated by Src kinases and serve as a docking point for phosphatases containing the src-homology 2 (SH2) domain. 8 Proteins containing consensus sequences for interaction with phosphorylated ITIMs include the SH2 domain-containing tyrosine phosphatase (SHP)-1, SHP-2, and the SH2 domain-containing inositol 5 ′ -phosphatase. 6 The recruitment of phosphatases to the J Leukoc Biol. 2019;106:957-966.

show abstract

CD300a expression is modulated in atopic dermatitis and could influence the inflammatory response

Cited by 16 publications

References 9 publications

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

DNA Methylation Levels in Mononuclear Leukocytes from the Mother and Her Child Are Associated with IgE Sensitization to Allergens in Early Life

A novel mast cell-dependent allergic peritonitis model

The immunoreceptor CD300a controls the intensity of inflammation and dysfunction in a model of Ag-induced arthritis in mice

Contact Info

Product

Resources

About