scholarly journals In chronic pancreatitis CD25+/Foxp3+ regulatory T-cells control pancreatic fibrosis by suppression of the type 2 immune response

2021 ◽  
Author(s):  
Juliane Glaubitz ◽  
Anika Wilden ◽  
Janine Golchert ◽  
Georg Homuth ◽  
Uwe Voelker ◽  
...  
Keyword(s):  
Immune Response ◽  
Chronic Pancreatitis ◽  
Disease Onset ◽  
Pancreatic Tissue ◽  
Lymphoid Cells ◽  
T Helper ◽  
Exocrine Insufficiency ◽  
Tissue Replacement ◽  
Type 2 Immune Response

Abstract Chronic pancreatitis (CP) is characterized by chronic inflammation and the progressive fibrotic replacement of exocrine and endocrine pancreatic tissue. We identified Tregs as central regulators of the fibroinflammatory reaction by a selective depletion of Foxp3-positive cells in a transgenic mouse model (DEREG-mice) of experimental CP. In Treg-depleted DEREG-mice, the induction of CP resulted in a significantly increased stroma deposition, the development of exocrine insufficiency and significant weight loss starting from day 14 after disease onset. In CP, Foxp3+/CD25+ Tregs suppress the type-2 immune response by a repression of Gata3+ T-helper cells (Th2), Gata3+ innate lymphoid cells type 2 (ILC2) and CD206+ M2-macrophages. A suspected pathomechanism behind the fibrotic tissue replacement may involve an observed dysbalance of Activin A expression in macrophages and of its counter regulator Follistatin. Our study identified Tregs as key regulators of the type-2 immune response and of organ remodeling during CP. The Treg-triggered immune response could be a therapeutic target to prevent fibrosis and preserve functional pancreatic tissue.

scholarly journals Immunization of BALB/c Mice with Killed Neospora caninum Tachyzoite Antigen Induces a Type 2 Immune Response and Exacerbates Encephalitis and Neurological Disease

2000 ◽  
Vol 7 (6) ◽  
pp. 893-898 ◽  
Author(s):  
Timothy V. Baszler ◽  
Terry F. McElwain ◽  
Bruce A. Mathison
Keyword(s):  
Immune Response ◽  
Neurological Disease ◽  
Neospora Caninum ◽  
Brain Lesions ◽  
Lymphoid Cells ◽  
Interleukin 4 ◽  
Type 2 Immune Response ◽  
Parasite Challenge

ABSTRACT BALB/c mice were immunized subcutaneously with solubleNeospora caninum tachyzoite antigen (NSO) entrapped in nonionic surfactant vesicles (NISVs) or administered with Freund's complete adjuvant (FCA). Following virulent parasite challenge, groups of mice immunized with NSO and either NISVs or FCA had clinical neurological disease and increased numbers of brain lesions compared to groups of mice inoculated with FCA, NISVs, or phosphate-buffered saline (PBS) alone. Increased numbers of brain lesions were statistically significant only between mice immunized with NISV-NSO and NISV- or PBS-treated mice. Following parasite challenge, brain inflammatory infiltrates in all experimental and control groups of mice were relatively similar and consisted of compact infiltrates of macrophages admixed with various numbers of lymphoid cells. Increased brain lesions in NSO-immunized mice were associated with increased antigen-specific interleukin 4 (IL-4) secretion and increased IL-4:gamma interferon secretion ratios from splenocytes in vitro and increased antigen-specific immunoglobulin G1 (IgG1):IgG2a ratios in vivo. Thus, immunization with whole killed N. caninum antigen and either liposoidal or Freund's adjuvant induced a type 2 immune response that was associated with worsened disease. The present studies emphasize the need to identify specific N. caninum antigens or other delivery systems that will elicit protective immune responses to neosporosis.

scholarly journals Imiquimod Does not Affect Shedding of Viable Chlamydiae in a Murine Model ofChlamydia trachomatisGenital Tract Infection

2003 ◽  
Vol 11 (2) ◽  
pp. 81-87 ◽  
Author(s):  
Kyle H. Ramsey ◽  
Namir Shaba ◽  
Kevin P. Cohoon ◽  
Kevin A. Ault
Keyword(s):  
Immune Response ◽  
Murine Model ◽  
Antibody Responses ◽  
Igg Subclass ◽  
T Helper ◽  
Type 2 Immune Response ◽  
Significant Difference ◽  
Helper Type

Objective:We postulated that either oral or vaginal administration of the immune response modifier imiquimod would decrease vaginal shedding ofChlamydia trachomatis, mouse pneumonitis strain (MoPn), in a murine model.Methods:Female BALB/c mice were infected intravaginally withC. trachomatis(MoPn) and were administered imiquimod either orally (30 mg/kg) or vaginally (10 μl of 5%imiquimod cream) prior to infection and every second day after infection for a total of four doses. The course of infection was monitored by collecting cervical–vaginal swabs and isolation in HeLa 229 cell culture. To determine whether the drug affected T helper type 1 or T helper type 2 immune response polarization, immunoglobulinG(IgG) subclass antibody responses were assessed at day 56 after infection.Results:There was no significant difference in the course of infection when imiquimod-treated mice were compared with sham-treated controls, regardless of whether the drug was administered orally or vaginally. IgG subclass antibody responses, and by extension, T helper type 1 to T helper type 2 immune response polarization, were also unaffected.Conclusions:Imiquimod has no efficacy in controllingC. trachomatis(MoPn) infection in the murine model.

scholarly journals Natural killer T cells are required for the development of a superantigen-driven T helper type 2 immune response in mice

Immunology ◽  
2005 ◽  
Vol 116 (2) ◽  
pp. 233-244 ◽  
Author(s):  
Auro Nomizo ◽  
Edilberto Postol ◽  
Raquel de Alencar ◽  
Fabiola Cardillo ◽  
Jose Mengel
Keyword(s):  
Immune Response ◽  
T Cells ◽  
Natural Killer ◽  
Natural Killer T Cells ◽  
T Helper ◽  
Type 2 Immune Response ◽  
Killer T Cells ◽  
Helper Type ◽  
Natural Killer T

scholarly journals Group 2 Innate Lymphoid Cells: A Double-Edged Sword in Cancer?

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3452
Author(s):  
Enrico Maggi ◽  
Irene Veneziani ◽  
Lorenzo Moretta ◽  
Lorenzo Cosmi ◽  
Francesco Annunziato
Keyword(s):  
Immune Response ◽  
Inflammatory Responses ◽  
Cell Subset ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Th2 Cell ◽  
Type 2 Immune Response ◽  
Group 2 ◽  
Lymphoid Organogenesis

Group 2 Innate Lymphoid Cells (ILC2s) belong to the family of helper ILCs which provide host defense against infectious agents, participate in inflammatory responses and mediate lymphoid organogenesis and tissue repair, mainly at the skin and mucosal level. Based on their transcriptional, phenotypic and functional profile, ILC2s mirror the features of the adaptive CD4+ Th2 cell subset, both contributing to the so-called type 2 immune response. Similar to other ILCs, ILC2s are rapidly activated by signals deriving from tissue and/or other tissue-resident immune cells. The biologic activity of ILCs needs to be tightly regulated in order to prevent them from contributing to severe inflammation and damage in several organs. Indeed, ILC2s display both enhancing and regulatory roles in several pathophysiological conditions, including tumors. In this review, we summarize the actual knowledge about ILC2s ability to induce or impair a protective immune response, their pro- or antitumor activity in murine models, human (children and adults) pathologies and the potential strategies to improve cancer immunotherapy by exploiting the features of ILC2s.

scholarly journals Anti-IL5 Drugs in COVID-19 Patients: Role of Eosinophils in SARS-CoV-2-Induced Immunopathology

2021 ◽  
Vol 12 ◽  
Author(s):  
Daniele Pala ◽  
Marco Pistis
Keyword(s):  
Immune Response ◽  
T Helper ◽  
T Helper 1 ◽  
Biological Drugs ◽  
T Helper 2 ◽  
Asthmatic Patients ◽  
Severe Asthmatic ◽  
Type 2 Cytokines ◽  
Type 2 Immune Response

SARS-CoV-2 infection stimulates a complex activation of the immune system. Eosinophils belong to the host’s defense equipment against respiratory viruses. In the first phase of the infection, eosinophils contribution is probably appropriate and beneficial, as they facilitate the suppression of the viral replication. However, in severe COVID-19 patients, during the second and third phases of the disease, eosinophils may participate in a maladaptive immune response and directly contribute to immunopathology. In fact, in severe patients, the immune response is prevalently T helper 1 type, but T helper 2 is also present. Eosinophils’ expansion and activation are stimulated by Type 2 cytokines, especially IL-5. Moreover, bronchial asthma, in which eosinophils play a central role, seems not to be a major risk factor for severe COVID-19. Among possible explanations, asthmatic patients are often treated with corticosteroids, which have been demonstrated to reduce the progression to critical COVID-19 in hospitalized patients. In addition to steroids, severe asthmatic patients are currently treated with biological drugs that target Type 2 immune response. Because IL-5 is necessary for the growth, survival, and activation of eosinophils, IL-5 inhibitors, such as mepolizumab, decrease the peripheral blood count of eosinophils, but do not influence eosinophils activation in the airway. In severe COVID-19 patients, the blockade of eosinophils’ activation might contrast harmful immunity.

scholarly journals IL-4–producing B cells regulate T helper cell dichotomy in type 1- and type 2-controlled diseases

2017 ◽  
Vol 114 (40) ◽  
pp. E8430-E8439 ◽  
Author(s):  
Ramona Hurdayal ◽  
Hlumani H. Ndlovu ◽  
Mélanie Revaz-Breton ◽  
Suraj P. Parihar ◽  
Justin Komguep Nono ◽  
...  
Keyword(s):  
Immune Response ◽  
B Cells ◽  
B Cell ◽  
Cutaneous Leishmaniasis ◽  
Leishmania Major ◽  
Interleukin 4 ◽  
T Helper ◽  
Type 2 Immune Response

Interleukin-4 (IL-4)–induced T helper (Th) 2 cells promote susceptibility to the protozoan parasite Leishmania major, while conferring immunity to the intestinal trematode Schistosoma mansoni. Here, we report that abrogation of IL-4 receptor alpha (IL-4Rα) signaling on B cells in BALB/c mice (mb1creIL-4Rα–/lox) transformed nonhealer BALB/c to a healer phenotype with an early type 1 and dramatically reduced type 2 immune response and an absence of ulceration and necrosis during cutaneous leishmaniasis. From adoptive reconstitution and mixed bone-marrow chimera studies in B cell-deficient (µMT) mice, we reveal a central role for B cell-derived IL-4 and IL-4Rα in the optimal induction of the susceptible type 2 phenotype to L. major infection. We further demonstrate that the absence of IL-4Rα signaling on B cells exacerbated S. mansoni-induced mortality and pathology in BALB/c mice, due to a diminished type 2 immune response. In both disease models, IL-4Rα–responsive B cells displayed increased IL-4 production as early as day 1 after infection. Together, these results demonstrate that IL-4–producing and IL-4Rα–responsive B cells are critical in regulating and assisting early T helper dichotomy toward Th2 responses, which are detrimental in cutaneous leishmaniasis but beneficial in acute schistosomiasis.

scholarly journals Maintenance of Type 2 Response by CXCR6-Deficient ILC2 in Papain-Induced Lung Inflammation

2019 ◽  
Vol 20 (21) ◽  
pp. 5493 ◽  
Author(s):  
Meunier ◽  
Chea ◽  
Garrido ◽  
Perchet ◽  
Petit ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Nk Cell ◽  
Lymphoid Cells ◽  
Inflammatory Conditions ◽  
Airway Diseases ◽  
Type 2 Cytokines ◽  
Lymphoid Organogenesis ◽  
Deficient Mice

Innate lymphoid cells (ILC) are important players of early immune defenses in situations like lymphoid organogenesis or in case of immune response to inflammation, infection and cancer. Th1 and Th2 antagonism is crucial for the regulation of immune responses, however mechanisms are still unclear for ILC functions. ILC2 and NK cells were reported to be both involved in allergic airway diseases and were shown to be able to interplay in the regulation of the immune response. CXCR6 is a common chemokine receptor expressed by all ILC, and its deficiency affects ILC2 and ILC1/NK cell numbers and functions in lungs in both steady-state and inflammatory conditions. We determined that the absence of a specific ILC2 KLRG1+ST2– subset in CXCR6-deficient mice is probably dependent on CXCR6 for its recruitment to the lung under inflammation. We show that despite their decreased numbers, lung CXCR6-deficient ILC2 are even more activated cells producing large amount of type 2 cytokines that could drive eosinophilia. This is strongly associated to the decrease of the lung Th1 response in CXCR6-deficient mice.

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