CD40 Expression by Human Bronchial Epithelial Cells

Gormand, F.; Brière, Francine; Peyrol, S; Raccurt, Mireille; Durand, Isabelle; Aït-Yahia, Smina; Lebecque, Serge; Banchereau, Jacques; Pachéco, Yves

doi:10.1046/j.1365-3083.1999.00510.x

Cited by 23 publications

(16 citation statements)

References 27 publications

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“…In preliminary studies, we had already demonstrated that 16HBE cells do not express CD40L, either under basal conditions or after oxidative stress (data not shown), and these data are supported by other evidence produced by Gormand and colleagues in 1999 (12). In this work, the authors demonstrated that immunostaining for CD40L was negative in bronchial epithelial cells.…”

Section: Discussionsupporting

confidence: 84%

“…We previously reported that CD40 and CD40L are expressed in bronchial epithelial cells of normal subjects and, to a greater extent, subjects with asthma (10). It has also been demonstrated that CD40 ligation can lead to the functional activation of bronchial epithelial cells and to the release of inflammatory mediators (11,12), which is related to NF-B activation (13). In these previous studies, the proinflammatory responses triggered by CD40 ligation were evaluated alone or in the presence of proinflammatory cytokines.…”

mentioning

confidence: 99%

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CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

Merendino

Bucchieri²,

Gagliardo³

et al. 2006

Am J Respir Cell Mol Biol

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CD40 and its ligand regulate pleiotropic biological responses, including cell proliferation, differentiation, and apoptosis. In many inflammatory lung diseases, tissue damage by environmental or endogenous oxidants plays a major role in disease pathogenesis. As the epithelial barrier is a major target for these oxidants, we postulated that CD40, the expression of which is increased in asthma, plays a role in the regulation of apoptosis of bronchial epithelial cells exposed to oxidants. Using 16HBE 14o؊ cells exposed to oxidant stress, we found that ligation of CD40 (induced by G28-5 monoclonal antibodies) enhanced cell survival and increased the number of cells in G2/M (interphase between DNA synthesis and mitosis) of the cell cycle. This was associated with NF-B and activator protein-1 activation and increased expression of the inhibitor of apoptosis, c-IAP1. However, oxidant stress-induced apoptosis was found to be caspase-and calpain-independent implicating CD40 ligation as a regulator of caspase-independent cell death. This was confirmed by the demonstration that CD40 ligation prevented mitochondrial release and nuclear translocation of apoptosis inducing factor. In conclusion, we demonstrate a novel role for CD40 as a regulator of epithelial cell survival against oxidant stress. Furthermore, we have identified, for the first time, an endogenous inhibitory pathway of caspase-independent cell death.

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Section: Discussionsupporting

confidence: 84%

mentioning

confidence: 99%

CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

Merendino

Bucchieri²,

Gagliardo³

et al. 2006

Am J Respir Cell Mol Biol

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“…Previous reports indicate that bronchial epithelial cells express CD40 (16,17). In particular, Gormand et al (17) have reported that the cytokines TNF-␣ and IFN-␥ increased the basal expression of CD40 on bronchial epithelial cell lines.…”

Section: Discussionmentioning

confidence: 95%

“…In particular, Gormand et al (17) have reported that the cytokines TNF-␣ and IFN-␥ increased the basal expression of CD40 on bronchial epithelial cell lines. Moreover, their data suggest that ligation of CD40 expressed on bronchial epithelial cell lines enhanced the expression of IL-6 and GM-CSF from these cells; however, CD40 engagement did not alter the sensitivity of these cells to the effects of TNF-␣ with regard to IL-6 and GM-CSF expression.…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory and Th2-Derived Cytokines Modulate CD40-Mediated Expression of Inflammatory Mediators in Airway Epithelia: Implications for the Role of Epithelial CD40 in Airway Inflammation

Propst

Denson

Rothstein

et al. 2000

The Journal of Immunology

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Cytokines produced by activated macrophages and Th2 cells within the lung play a key role in asthma-associated airway inflammation. Additionally, recent studies suggest that the molecule CD40 modulates lung immune responses. Because airway epithelial cells can act as immune effector cells through the expression of inflammatory mediators, the epithelium is now considered important in the generation of asthma-associated inflammation. Therefore, the goal of the present study was to examine the effects of proinflammatory and Th2-derived cytokines on the function of CD40 in airway epithelia. The results show that airway epithelial cells express CD40 and that engagement of epithelial CD40 induces a significant increase in expression of the chemokines RANTES, monocyte chemoattractant protein (MCP-1), and IL-8 and the adhesion molecule ICAM-1. Cross-linking epithelial CD40 had no effect on expression of the adhesion molecule VCAM-1. The proinflammatory cytokines TNF-α and IL-1β and the Th2-derived cytokines IL-4 and IL-13 modulated the positive effects of CD40 engagement on inflammatory mediator expression in airway epithelial cells. Importantly, CD40 ligation enhanced the sensitivity of airway epithelial cells to the effects of TNF-α and/or IL-1β on expression of RANTES, MCP-1, IL-8, and VCAM-1. In contrast, neither IL-4 nor IL-13 modified the effects of CD40 engagement on the expression of RANTES, MCP-1, IL-8, or VCAM-1; however, both IL-4 and IL-13 attenuated the effects of CD40 cross-linking on ICAM-1 expression. Together, these findings suggest that interactions between CD40-responsive airway epithelial cells and CD40 ligand+ leukocytes, such as activated T cells, eosinophils, and mast cells, modulate asthma-associated airway inflammation.

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“…CD40 is mostly expressed on antigen-presenting cells (APCs) like dendritic cells (DCs), monocytes, 5 as well as non-hematopoietic cells such as fibroblasts and epithelial cells. 6 Its ligand CD40L (CD154) is preferentially expressed on activated T cells, especially the CD4 subset, 7 and in an inflammatory setting is also induced on monocytic cells, 5 NK cells, 8 mast cells and basophils. 9 CD40–CD40L interaction plays a major role in CD4 B-cell collaboration, and abrogation of this pathway leads to the failure of germinal center formation, memory B-cell activation, and somatic hypermutation.…”

Section: Introductionmentioning

confidence: 99%

CD40 Signaling to the Rescue: A CD8 Exhaustion Perspective in Chronic Infectious Diseases

2013

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Chronic infectious diseases such as HIV, HBV, and HCV, among others, cause severe morbidity and mortality globally. Progressive decline in CD8 functionality, survival, and proliferative potential—a phenomenon referred to as CD8 exhaustion—is believed to be responsible for poor pathogen control in chronic infectious diseases. While the role of negative inhibitory receptors such as PD-1 in augmenting CD8 exhaustion has been extensively studied, the role of positive costimulatory receptors remains poorly understood. In this review, we discuss how one such costimulatory pathway, CD40–CD40L, regulates CD8 dysfunction and rescue. While the significance of this pathway has been extensively investigated in models of autoimmunity, acute infectious diseases, and tumor models, the role played by CD40–CD40L in regulating CD8 exhaustion in chronic infectious diseases is just beginning to be understood. Considering that monotherapy with blocking antibodies targeting inhibitory PD-1-PD-L1 pathway is only partially effective at ameliorating CD8 exhaustion and that humanized CD40 agonist antibodies are currently available, a better understanding of the role of the CD40–CD40L pathway in chronic infectious diseases will pave the way for the development of more robust immunotherapeutic and prophylactic vaccination strategies.

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CD40 Expression by Human Bronchial Epithelial Cells

Cited by 23 publications

References 27 publications

CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

CD40 Ligation Protects Bronchial Epithelium against Oxidant-Induced Caspase-Independent Cell Death

Proinflammatory and Th2-Derived Cytokines Modulate CD40-Mediated Expression of Inflammatory Mediators in Airway Epithelia: Implications for the Role of Epithelial CD40 in Airway Inflammation

CD40 Signaling to the Rescue: A CD8 Exhaustion Perspective in Chronic Infectious Diseases

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