CD45RB Ligation Inhibits Allergic Pulmonary Inflammation by Inducing CTLA4 Transcription

Jen, Kai Yu; Campo, Monica; He, Hongzhen; Makani, Samir; Velasco, German; Rothstein, David M.; Perkins, David L.

doi:10.4049/jimmunol.179.6.4212

Cited by 19 publications

(21 citation statements)

References 44 publications

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“…37,38 Blockade of CTLA-4 in animal models has been shown to maintain or increase allergic responses and inflammation, 39 with increased eosinophil numbers, IgE levels, and allergen-induced IL-13 levels, whereas increased CTLA-4 expression inhibits allergic pulmonary inflammation. 40 In addition, CTLA-4 can efficiently inhibit inflammatory responses in human subjects in vivo, as evidenced by the successful treatment of chronic inflammatory diseases by the CTLA-4-immunoglobulin fusion protein abatacept. 41,42 The 39-UTR of the CTLA-4 transcript contains an evolutionarily conserved miR-155 binding site, and we found that mutation of this site abolished miR-155-mediated suppression of CTLA-4, as demonstrated by luciferase reporter assays.…”

Section: Discussionmentioning

confidence: 99%

MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

Sonkoly¹,

Janson²,

Majuri³

et al. 2010

Journal of Allergy and Clinical Immunology

275

247

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Section: Discussionmentioning

confidence: 99%

MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

Sonkoly¹,

Janson²,

Majuri³

et al. 2010

Journal of Allergy and Clinical Immunology

275

247

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“…Understanding the molecular mechanisms behind RB-associated correlations (and RO) would better facilitate the design of CD45-based therapeutic approaches against disease. Antibodies against RB have been shown to have both an immunosuppressive [37][38][39] and stimulatory 40,41 effect on lymphoid cell behavior depending on various environmental factors, including differential associations with multiple surface molecules. 42,43 Anti-RB treatment is useful as an immunotherapeutic agent and induces transplant tolerance.…”

Section: Discussionmentioning

confidence: 99%

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Jackson

Harp

Patel

et al. 2009

Blood

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We previously reported that RO ؉ expression correlated with increased mutation, activation, and selection among human germinal center (GC) B cells. Here, we subdivided human tonsillar B cells, including IgD ؊ CD38 ؉ GC B cells, into different fractions based on RB expression. Although each subset contained RB ؉ cells, when used as an intrasubset marker, differential RB expression effectively discriminated between phenotypically distinct cells. For example, RB ؉ GC B cells were enriched for activated cells with lower AID expression. RB inversely correlated with mutation frequency, demonstrating a key difference between RB-and RO-expressing GC B cells. Reduced RB expression during the transition from pre-GC (IgM ؉ IgD ؉ CD38 ؉ CD27 ؊ ) to GCB cells was followed by a dramatic increase during the GC-to-plasmablast (IgD ؊ CD38 ؉؉ CD27 ؉ ) and memory (IgD ؊ CD38 ؊ CD27 ؉ ) transition. Interestingly, RB ؉ GC B cells showed increased signs of terminal differentiation toward CD27 ؉ post-GC early plasmablast (increased CD38 and RO) or early memory IntroductionImmune function is uncompromisingly governed by at least 3 interdependent principles including recognition, effector function, and transition. Early naive B and T cells that successfully bind foreign antigen become activated and undergo developmental transition toward more mature, faster responding memory subsets. In contrast, lymphocytes that bind self-antigen in the periphery are usually counterselected against and undergo a different type of transition, one toward apoptosis or anergy. Ineffectual negative selection against self-specific B cells has been associated with the development of autoimmune and neoplastic diseases. Unfortunately, potential factors responsible for the redirection or abrogation of transitions toward cell death and anergy have not been conclusively determined. Antibody sequence analyses revealed that B cells participating in autoreactive responses are often mutated and show signs of selection for self-antigen. 1,2 This suggests that somatic hypermutation (SHM) during proliferation and activationbased transitions in the dynamic germinal center reaction may play a role (whether direct or indirect) in disease pathogenesis.We therefore sought to develop an expedient approach that would allow for the reproducible identification of B-cell populations that exist at different transitional stages based on their states of activation, SHM-dependent diversification, and developmental progression toward adjacent downstream subsets. Delineating how surface marker profiles change as B cells transition between key stages (especially when immunoregulatory markers such as CD45 protein tyrosine phosphatase are included in such profiles) should increase our understanding of B-cell development and ultimately how to circumvent dysregulated processes that could lead to disease.Over the past 3 decades, our research laboratory has investigated multiple aspects of human B-cell development and the molecular processes that collectively shape the peripheral BCR repertoi...

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“…Recently, Jen and colleagues (31) demonstrated that blocking CD45RB with a CD45RB antagonist resulted in a substantial increase in airway inflammation. However, the administration of a CD45RB agonist caused a significant decrease in airway inflammation and a substantial increase of CTLA-4 mRNA expression.…”

Section: Discussionmentioning

confidence: 99%

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

McGee¹,

Yagita²,

Shao³

et al. 2010

Am J Respir Cell Mol Biol

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We recently reported that the adoptive transfer of T-regulatory cells (Tregs) isolated from lung and spleen tissue of green fluorescent protein-transgenic mice reversed airway hyperresponsiveness and airway inflammation. Because Programmed Death-1 (PD-1) is a pivotal receptor regulating effector T-cell activation by Tregs, we evaluated whether PD-1 is involved in the therapeutic effect of naturally occurring Tregs (NTregs) and inducible Tregs (iTregs) in cockroach (CRA)-sensitized and challenged mice. The CD4 1 CD25 1 NTregs and CD4 1 CD25 2 iTregs isolated from the lungs and spleens of BALB/c mice were adoptively transferred into CRA-sensitized and CRA-challenged mice with and without anti-PD-1 antibody (100 mg/ mice). The CD4 1 CD25 1 T cells in the lung were phenotyped after adoptive transfer. Concentrations of IL-4, IL-5, IL-10, IFN-g, and IL-13 in bronchoalveolar lavage fluid (BALF) were measured using ELISA. The NTregs and iTregs from either lung or spleen tissue reversed airway hyperresponsiveness for at least 4 wk. However, the therapeutic effect was blocked by administering the anti-PD-1 antibody. The administration of Tregs-recipient mice with anti-PD-1 antibody significantly decreased cytotoxic T-lymphocyte antigen-4 expression, with low concentrations of Forkhead-winged transcriptional factor box 3 (Foxp3) mRNA transcripts in lung CD4 1 CD25 1 T cells. These mice had substantially higher concentrations of BALF IL-4, IL-5, and IL-13, but significantly decreased levels of BALF IL-10. Adoptive therapy recipients without the anti-PD-1 antibody exhibited high levels of CTLA-4 expression and Foxp3 transcripts in lung CD4 1 CD25 1 T cells, with a significant decrease in BALF IL-4, IL-5, and IL-13 concentrations and a substantial increase in BALF IL-10 concentrations. These data suggest that the reversal of airway hyperresponsiveness and airway inflammation by Tregs is mediated in part by PD-1, because other costimulatory molecules (e.g., inducible costimulatory molecule [ICOS] or CTLA-4) have been shown to play a role in Treg-mediated suppression.

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CD45RB Ligation Inhibits Allergic Pulmonary Inflammation by Inducing CTLA4 Transcription

Cited by 19 publications

References 44 publications

MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

MiR-155 is overexpressed in patients with atopic dermatitis and modulates T-cell proliferative responses by targeting cytotoxic T lymphocyte–associated antigen 4

Key developmental transitions in human germinal center B cells are revealed by differential CD45RB expression

Programmed Death-1 Antibody Blocks Therapeutic Effects of T-Regulatory Cells in Cockroach Antigen-Induced Allergic Asthma

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