scholarly journals Case Report: Hyper IgE, but Not the Usual Suspects–Kimura Disease in an Adolescent Female

2021 ◽  
Vol 9 ◽  
Author(s):  
Prasanna Venkatesh Ramachandran ◽  
C. Mary Healy ◽  
Elton M. Lambert ◽  
Deyanara Guerra ◽  
Choladda V. Curry ◽  
...  
Keyword(s):  
Inborn Error ◽  
Cell Activation ◽  
Immunoglobulin E ◽  
Neck Mass ◽  
Adolescent Female ◽  
T Helper ◽  
Kimura Disease ◽  
Th2 Cell ◽  
Histopathologic Evaluation

Elevated immunoglobulin E (IgE) levels can be associated with infectious, allergic and inflammatory disorders, and rarely as a manifestation of an inborn error of immunity. Here we report the case of an adolescent female who presented with a gradually enlarging neck mass, lymphadenopathy, eosinophilia and highly elevated IgE levels. Laboratory and histopathologic evaluation revealed an unlikely diagnosis of Kimura Disease. We discuss the differential diagnosis of a neck mass with prominent eosinophils on histology, and review support for T-helper type 2 (Th2) cell activation and hyper-IgE in Kimura Disease.

scholarly journals Simultaneous Disruption of Interleukin (IL)-4 and IL-13 Defines Individual Roles in T Helper Cell Type 2–mediated Responses

1999 ◽  
Vol 189 (10) ◽  
pp. 1565-1572 ◽  
Author(s):  
Grahame J. McKenzie ◽  
Padraic G. Fallon ◽  
Claire L. Emson ◽  
Richard K. Grencis ◽  
Andrew N.J. McKenzie
Keyword(s):  
Immunoglobulin E ◽  
Gastrointestinal Nematode ◽  
Eosinophil Infiltration ◽  
Nippostrongylus Brasiliensis ◽  
T Helper ◽  
Compensatory Mechanisms ◽  
Th2 Cell ◽  
Vector Targeting ◽  
Deficient Mice

Using a single vector targeting strategy, we have generated mice with a combined deficiency of interleukin (IL)-4 and IL-13 to clarify their roles in T helper type 2 (Th2) cell responses. Using immunological challenges normally characterized by a Th2-like response, we have compared the responses of the double-deficient mice with those generated by wild-type, IL-4–deficient, and IL-13–deficient mice. Using a pulmonary granuloma model, induced with Schistosoma mansoni eggs, we demonstrate that although eosinophil infiltration, immunoglobulin E, and IL-5 production are reduced in the IL-4–deficient mice and IL-13–deficient mice, they are abolished only in the combined absence of both cytokines. Furthermore, IL-4/13–deficient animals are severely impaired in their ability to expel the gastrointestinal nematode Nippostrongylus brasiliensis. Unexpectedly, N. brasiliensis–infected IL-4/13–deficient mice developed elevated IL-5 and eosinophilia, indicating that compensatory mechanisms exist for the expression of IL-5, although serum IgE remained undetectable. IL-4/13–deficient mice default to a Th1-like phenotype characterized by the expression of interferon γ and the production of IgG2a and IgG2b. We conclude that IL-4 and IL-13 cooperate to initiate rapid Th2 cell–driven responses, and that although their functions overlap, they perform additive roles.

scholarly journals Critical Involvement of CD44 in T Helper Type 2 Cell-Mediated Eosinophilic Airway Inflammation in a Mouse Model of Acute Asthma

2022 ◽  
Vol 12 ◽  
Author(s):  
Shigeki Katoh
Keyword(s):  
Monoclonal Antibodies ◽  
Airway Inflammation ◽  
Th17 Cells ◽  
Acute Asthma ◽  
Mite Allergen ◽  
Th2 Cells ◽  
T Helper ◽  
Th2 Cell ◽  
Helper Type

Interactions between CD44 and hyaluronan (HA) are crucial for recruiting leukocytes to inflamed tissues. This review summarizes findings from our studies of the roles of CD44-HA interactions in leukocyte trafficking, with a particular focus on airway T helper type 2 (Th2) cells in mouse models of acute asthma. In a mite allergen-induced model of acute asthma, intraperitoneal injection of anti-CD44 monoclonal antibodies blocked lymphocytes and eosinophils from accumulating in the lung, and suppressed both the antigen-induced increase in Th2 cytokines in the bronchoalveolar lavage fluid (BALF) and airway hyperresponsiveness (AHR). CD44 deficiency was associated with decreased mite allergen-induced Th2 cell-mediated airway inflammation and AHR in sensitized mice. Asthmatic responses to antigen-sensitized splenic CD4+ T cells transferred from CD44-deficient mice were weaker than in wild-type mice. Administration of anti-CD44 monoclonal antibodies preferentially suppressed the airway accumulation of antigen-specific Th2 cells induced by antigen challenge, without affecting Th1 and Th17 cells. Increased HA-binding ability of CD44 and expression of Neu1 sialidase were observed on antigen-specific Th2 cells compared with antigen-specific Th1 and Th17 cells. Finally, in a mouse model of acute asthma, neuraminidase 1-deficient SM/J mice exhibited a lower Th2 cytokine concentration and a lower absolute Th2 cell number in the BALF, as well as an attenuated AHR. Our findings indicate that CD44 critically contributes to the antigen challenge-induced airway accumulation of antigen-specific Th2 cells, without affecting Th1 and Th17 cells, in mice. Furthermore, neuraminidase 1 activity is necessary for the interaction between HA and CD44, and Th2 cell-mediated airway inflammation.

scholarly journals No audible wheezing

2005 ◽  
Vol 201 (12) ◽  
pp. 1869-1873 ◽  
Author(s):  
Joshua A. Boyce ◽  
K. Frank Austen
Keyword(s):  
Mast Cells ◽  
Mouse Models ◽  
Airway Hyperresponsiveness ◽  
Pulmonary Inflammation ◽  
Genetic Differences ◽  
Mouse Strains ◽  
T Helper ◽  
Th2 Cell ◽  
Helper Type

Mouse models of T helper type 2 (Th2) cell–biased pulmonary inflammation have elucidated mechanisms of sensitization, cell traffic, and induced airway hyperresponsiveness (AHR). Nonetheless, most mice lack intrinsic AHR, a central property of human asthma, and disparities persist regarding the contributions of eosinophils and mast cells and the sensitivity to induced AHR in the commonly used mouse strains. We suggest that these discordances, reflecting methodological and genetic differences, may be informative for understanding heterogeneity of human asthma.

scholarly journals Immunostimulatory oligonucleotides block allergic airway inflammation by inhibiting Th2 cell activation and IgE-mediated cytokine induction

2005 ◽  
Vol 202 (11) ◽  
pp. 1563-1573 ◽  
Author(s):  
Edith M. Hessel ◽  
Mabel Chu ◽  
Jennifer O. Lizcano ◽  
Bonnie Chang ◽  
Nancy Herman ◽  
...  
Keyword(s):  
Cell Activation ◽  
Immunoglobulin E ◽  
Allergen Challenge ◽  
Allergic Airway Inflammation ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Functional Responses ◽  
Th2 Response ◽  
Airway Responses

A single treatment with a CpG-containing immunostimulatory DNA sequence (ISS) given before allergen challenge can inhibit T helper type 2 cell (Th2)–mediated airway responses in animal models of allergic asthma; however, the mechanism of this inhibition remains largely undefined. Here, we demonstrate that airway delivery of ISS before allergen challenge in Th2-primed mice acts in two distinct ways to prevent the allergic responses to this challenge. The first is to prevent induction of cytokines from allergen-specific Th2 cells, as demonstrated by the nearly complete inhibition of Th2 cytokine production, Th2-dependent functional responses, and gene induction patterns. ISS inhibits the Th2 response by rendering lung antigen-presenting cells (APCs) unable to effectively present antigen to Th2 cells, but not to Th1 cells. This loss of APC function correlates with a reduced expression of costimulatory molecules, including programmed cell death ligand (PD-L)1, PD-L2, CD40, CD80, CD86, and inducible T cell costimulator, and of major histocompatibility complex class II on CD11c+APCs from the airways of ISS-treated mice. The second important action of ISS is inhibition of immunoglobulin E–dependent release of Th2 cytokines, especially interleukin 4, from basophils and/or mast cells in the airways of Th2-primed mice. Thus, inhibition by ISS of allergic responses can be explained by two novel mechanisms that culminate in the inhibition of the principal sources of type 2 cytokines in the airways.

scholarly journals Essential Role of Lung Plasmacytoid Dendritic Cells in Preventing Asthmatic Reactions to Harmless Inhaled Antigen

2004 ◽  
Vol 200 (1) ◽  
pp. 89-98 ◽  
Author(s):  
Hendrik Jan de Heer ◽  
Hamida Hammad ◽  
Thomas Soullié ◽  
Daniëlle Hijdra ◽  
Nanda Vos ◽  
...  
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Inflammatory Responses ◽  
Immunoglobulin E ◽  
Atopic Asthma ◽  
Cell Hyperplasia ◽  
Asthma Model ◽  
Th2 Cell

Tolerance is the usual outcome of inhalation of harmless antigen, yet T helper (Th) type 2 cell sensitization to inhaled allergens induced by dendritic cells (DCs) is common in atopic asthma. Here, we show that both myeloid (m) and plasmacytoid (p) DCs take up inhaled antigen in the lung and present it in an immunogenic or tolerogenic form to draining node T cells. Strikingly, depletion of pDCs during inhalation of normally inert antigen led to immunoglobulin E sensitization, airway eosinophilia, goblet cell hyperplasia, and Th2 cell cytokine production, cardinal features of asthma. Furthermore, adoptive transfer of pDCs before sensitization prevented disease in a mouse asthma model. On a functional level, pDCs did not induce T cell division but suppressed the generation of effector T cells induced by mDCs. These studies show that pDCs provide intrinsic protection against inflammatory responses to harmless antigen. Therapies exploiting pDC function might be clinically effective in preventing the development of asthma.

Down-regulation of murine susceptibility to cerebral malaria by inoculation with third-stage larvae of the filarial nematode Brugia pahangi

Parasitology ◽  
1997 ◽  
Vol 114 (4) ◽  
pp. 333-338 ◽  
Author(s):  
Y. YAN ◽  
G. INUO ◽  
N. AKAO ◽  
S. TSUKIDATE ◽  
K. FUJITA
Keyword(s):  
Cerebral Malaria ◽  
Cytokine Production ◽  
Severe Anaemia ◽  
T Helper ◽  
Brugia Pahangi ◽  
Th2 Cell ◽  
Helminthic Infections ◽  
Filarial Antigen ◽  
Third Stage

In areas where malaria is endemic, helminthic infections, caused by intestinal or filarial parasites, commonly coexist with malaria in the same individual. This study investigates the course of Plasmodium berghei malaria infection in CBA/J mice inoculated with irradiated attenuated 3rd-stage larvae (L3) of Brugia pahangi. Peripheral eosinophil counts, serum IgE levels and cytokine production revealed that the filarial antigen induced T-helper type 2 (Th2) cell predominance in these mice, which protected them against the development of cerebral malaria. These mice significantly prolonged their survival, compared with the control mice after P. berghei infection. All of the mice not inoculated with irradiated L3 died within 12 days with acute neurological manifestations unrelated to the level of parasitaemia after infection of P. berghei. Conversely, most of the inoculated mice lived more than 3 weeks following infection with P. berghei, dying in the fourth week of severe anaemia and overwhelming parasitaemia. This suggests that Th2-dominant responses lead to the downregulation of susceptibility to murine cerebral malaria.

scholarly journals Understanding the Generation and Regulation of IL-4 Producing T Helper 2 Cells

2021 ◽  
Author(s):  
◽  
Helen Mearns
Keyword(s):  
Cell Activity ◽  
Physiological Role ◽  
Th2 Cells ◽  
Total Serum ◽  
T Helper ◽  
Th2 Response ◽  
Th2 Cell ◽  
Reporter Mice

<p>A keenly sought therapeutic approach for the treatment of allergic disease is the identification and neutralization of the cytokine that regulates the differentiation of Th2 cells. Th2 cells are CD4 T cells differentiated to secrete IL-4. These cells are exciting new targets for asthma therapies due to the key role they play in allergic airway diseases. Recently the cytokine IL-25 has been shown to enhance Th2 cell activity and play important roles in mediating allergic inflammatory responses. To investigate this further we crossed IL-25 deficient mice with GFP-IL-4 reporter mice and developed an assay of in vitro and in vivo IL-4 independent Th2 differentiation. These assays were used to determine whether IL-25 was critical for the formation of Th2 cells. We found there was no physiological role for IL-25 in either the differentiation of Th2 cells or their development to effector or memory Th2 subsets. In the strong Th2 setting of a helminth infection the absence of IL-25 resulted in no defects in the effector type 2 responses associated with T helper type 2 immunity including, mucous hyperplasia, class switching to IgE and protection against challenge infections. Importantly this data challenges the newly found and growing status of the cytokine IL-25 and its proposed role in promoting Th2 responses. The second part of this thesis investigated whether the genomic organisation, which reflects commitment to Th2 cytokine expression, could provide a clearer definition of a functional in vivo Th2 cell. Two distinct IL-4 reporter mice were crossed and Th2 in vivo assays were developed that allowed tracking of the individual alleles of IL-4 in a variety of tissue types and Th2 subsets. Interestingly in vivo expression of IL-4 is mostly monoallelic yet there is a small highly activated population of biallelic IL-4 expressing Th2 cells. Physiologically each allele of IL-4 was required for a functional Th2 response with total serum IgE titres up to 4 fold lower in IL-4+/- heterozygous compared to the IL-4+/+ sufficient animals and a significant loss in protective immunity against challenge infections with helminths occurred in the IL-4+/- heterozygous animals. The similarity in deficiencies in Th2 immunity in the IL-4+/- heterozygous and IL-4-/- deficient compared to the IL-4+/+ sufficient animals lead to the proposal that the generation of biallelic Th2 cells may be required for specialised cell-to-cell mediated delivery of tailored activation signals and higher quantities of IL-4 required to mediate fully developed Th2 immune responses.</p>

scholarly journals Ginsenoside Rh2 Ameliorates Atopic Dermatitis in NC/Nga Mice by Suppressing NF-kappaB-Mediated Thymic Stromal Lymphopoietin Expression and T Helper Type 2 Differentiation

2019 ◽  
Vol 20 (24) ◽  
pp. 6111 ◽  
Author(s):  
Eunsu Ko ◽  
Sungjoo Park ◽  
Jun Hyoung Lee ◽  
Chang-Hao Cui ◽  
Jingang Hou ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Immunoglobulin E ◽  
Thymic Stromal Lymphopoietin ◽  
Ginsenoside Rh2 ◽  
T Helper ◽  
Polycytidylic Acid ◽  
Anti Inflammatory ◽  
Helper Type

Ginsenosides are known to have various highly pharmacological activities, such as anti-cancer and anti-inflammatory effects. However, the search for the most effective ginsenosides against the pathogenesis of atopic dermatitis (AD) and the study of the effects of ginsenosides on specific cytokines involved in AD remain unclear. In this study, ginsenoside Rh2 was shown to exert the most effective anti-inflammatory action on thymic stromal lymphopoietin (TSLP) and interleukin 8 in tumor necrosis factor-alpha and polyinosinic: polycytidylic acid induced normal human keratinocytes by inhibiting proinflammatory cytokines at both protein and transcriptional levels. Concomitantly, Rh2 also efficiently alleviated 2,4-dinitrochlorobenzene-induced AD-like skin symptoms when applied topically, including suppression of immune cell infiltration, cytokine expression, and serum immunoglobulin E levels in NC/Nga mice. In line with the in vitro results, Rh2 inhibited TSLP levels in AD mice via regulation of an underlying mechanism involving the nuclear factor κB pathways. In addition, in regard to immune cells, we showed that Rh2 suppressed not only the expression of TSLP but the differentiation of naïve CD4+ T-cells into T helper type 2 cells and their effector function in vitro. Collectively, our results indicated that Rh2 might be considered as a good therapeutic candidate for the alternative treatment of AD.

Sign in / Sign up

Export Citation Format

Share Document