Apoptosis and Engulfment by Bronchial Epithelial Cells. Implications for Allergic Airway Inflammation

Penberthy, Kristen K.; Juncadella, Ignacio J.; Ravichandran, Kodi S.

doi:10.1513/annalsats.201405-200aw

Cited by 29 publications

(22 citation statements)

References 26 publications

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“…Additionally, recognition of different antigen-bearing APCs may allow a diverse repertoire of CD4 cells to expand within the lung or persist, albeit in lower numbers, at memory. It is known that there is a wide variety of MHC class II ϩ APCs that are positioned differently throughout the lung (13,(46)(47)(48). Therefore, a CD4 T cell repertoire encompassing many viral epitopes may ensure optimal recognition of distinct antigen-bearing cells.…”

Section: Discussionmentioning

confidence: 99%

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection

DiPiazza

Laniewski

Rattan

et al. 2018

J Virol

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Pulmonary CD4 T cells are critical in respiratory virus control, both by delivering direct effector function and through coordinating responses of other immune cells. Recent studies have shown that following influenza virus infection, virus-specific CD4 T cells are partitioned between pulmonary vasculature and lung tissue. However, very little is known about the peptide specificity or functional differences of CD4 T cells within these two compartments. Using a mouse model of influenza virus infection in conjunction with intravascular labeling , the cell surface phenotype, epitope specificity, and functional potential of the endogenous polyclonal CD4 T cell response was examined by tracking nine independent CD4 T cell epitope specificities. These studies revealed that tissue-localized CD4 cells were globally distinct from vascular cells in expression of markers associated with transendothelial migration, residency, and micropositioning. Despite these differences, there was little evidence for remodeling of the viral epitope specificity or cytokine potential as cells transition from vasculature to the highly inflamed lung tissue. Our studies also distinguished cells in the pulmonary vasculature from peripheral circulating CD4 T cells, providing support for the concept that the pulmonary vasculature does not simply reflect circulating cells that are trapped within the narrow confines of capillary vessels but rather is enriched in transitional cells primed in the draining lymph node that have specialized potential to enter the lung tissue. CD4 T cells convey a multitude of functions in immunity to influenza, including those delivered in the lymph node and others conveyed by CD4 T cells that leave the lymph node, enter the blood, and extravasate into the lung tissue. Here, we show that the transition of recently primed CD4 cells detected in the lung vasculature undergo profound changes in expression of markers associated with tissue localization as they establish residence in the lung. However, this transition does not edit CD4 T cell epitope specificity or the cytokine potential of the CD4 T cells. Thus, CD4 T cells that enter the infected lung can convey diverse functions and have a sufficiently broad viral antigen specificity to detect the complex array of infected cells within the infected tissue, offering the potential for more effective protective function.

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Section: Discussionmentioning

confidence: 99%

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection

DiPiazza

Laniewski

Rattan

et al. 2018

J Virol

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“…Upon pathogen clearance, the epithelium also contributes to clearance of the infiltrated immune cells. Conventionally, macrophages have been credited to clear the dead cells present in the lung post inflammatory response; however, recent studies have also implicated important roles of the lung epithelium in clearing the dead cells and cellular debris from the lung and preventing persistent inflammation (58). Blocking epithelial phagocytosis by inducible mutation of small GTPase Rac1 leads to persistent lung inflammation (23).…”

Section: Recruitment Of Immune Cellsmentioning

confidence: 99%

Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens

et al. 2020

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Bacterial lung infections are major healthcare challenges killing millions of people worldwide and resulting in a huge economic burden. Both basic and clinical research have elucidated host mechanisms that contribute to the bacterial clearance where an indispensable role of immune cells has been established. However, the role of respiratory epithelial cells in bacterial clearance has garnered limited attention due to their weak inflammatory or phagocytic ability compared to immune cells such as macrophages and neutrophils. These studies often underappreciate the fact that epithelial cells are the most abundant cells in the lung, not only serving as building blocks but also providing immune protection throughout the lung. Epithelial cells function either independently to eradicate the pathogen or communicate with immune cells to orchestrate pathogen clearance. The epithelial cells have multiple mechanisms that include mucus production, antimicrobial peptide production, muco-ciliary clearance, and phagocytosis, all of which contribute to their direct antibacterial function. Secretion of cytokines to recruit immune cells and potentiate their antimicrobial activities is a pathway by which the epithelium contributes to bacterial clearance. Successful pathogens outsmart epithelial resistance and find a way to replicate in sufficient numbers to establish infections in the airway or lung epithelial surfaces. In this mini-review, we discuss evidences that establish important roles for epithelial host defense against invading respiratory bacterial pathogens and demonstrate how pathogens outsmart these epithelial immune mechanisms to successfully establish infection. Finally, we discuss briefly how to boost epithelial immunity to improve outcomes in bacterial lung infections.

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“…Phosphatidylserine (PS), normally found on the inner leaflet of the plasma membrane, is exposed at the cell surface of apoptotic cells. PS is directly recognized by several receptors, such as stabilin 2, BAI1, and Tim‐4, or indirectly by MerKT or αvβ5 integrin . These receptors can cooperate to mediate an immunologically silent removal of dying cells by phagocytes, with secretion of anti‐inflammatory cytokines, leading to regulatory T cells differentiation/expansion and active tolerance induction.…”

Section: Introductionmentioning

confidence: 99%

“…PS is directly recognized by several receptors, such as stabilin 2, BAI1, and Tim-4, or indirectly by MerKT or αvβ5 integrin. 27 These receptors can cooperate to mediate an immunologically silent removal of dying cells by phagocytes, with secretion of anti-inflammatory cytokines, leading to regulatory T cells differentiation/expansion and active tolerance induction. Some of these PS receptors belong to the scavenger receptors (SR) family, 28,29 which are predominantly expressed by myeloid cells.…”

Section: Introductionmentioning

confidence: 99%

In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis

Coppard

Hannani

Humbert

et al. 2019

J of Clinical Apheresis

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Background Extracorporeal photopheresis (ECP) is an effective therapy for graft vs host disease (GVHD), based on infusion of UVA‐irradiated and 8 methoxy‐psoralen (PUVA)‐treated leukocytes. Reinfusion of these apoptosing cells affects the functionality of pathogenic T cells through poorly understood immunomodulatory mechanisms. Apoptosis is usually a silent, tolerance‐associated process, but can also be immunogenic, depending on death‐inducers and environmental context. Methods To understand ECP mechanisms of action, human alloreactive T cells generated in an in vitro model mimicking GVHD were used, as well as primary cells from GVHD patients. Cells were submitted to PUVA treatment and their phenotype and immunogenicity were analyzed, using cell culture and flow cytometry. Results In vitro PUVA treatment induced the expression of several damage‐associated molecular patterns (DAMPs) by dying T cells (calreticulin, high‐mobility group box‐1, and to a lesser extent heat shock proteins 70 and 90), especially upon T cell activation, leading to their phagocytosis by macrophages and dendritic cells (DCs). Allogeneic DCs preincubated with PUVA treated T cells induced comparable naive T cell proliferation and polarization as control allogeneic DC. Conclusion Altogether, in our experimental settings, in vitro PUVA‐treatment induces a partially immunogenic phenotype allowing phagocytosis of apoptotic cells by macrophages and DC, however not sufficient to induce dendritic cell maturation and T cell activation. These data refine current models of ECP‐mediated immune modulation and emphasize the need to further analyze PUVA‐treated cell interactions with immune cells.

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Apoptosis and Engulfment by Bronchial Epithelial Cells. Implications for Allergic Airway Inflammation

Cited by 29 publications

References 26 publications

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection

CD4 T Cell Epitope Specificity and Cytokine Potential Are Preserved as Cells Transition from the Lung Vasculature to Lung Tissue following Influenza Virus Infection

Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens

In vitro PUVA treatment triggers calreticulin exposition and HMGB1 release by dying T lymphocytes in GVHD: New insights in extracorporeal photopheresis

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