Protective role of B cells in sterile particulate–induced lung injury

Atif, Shaikh M.; Mack, Douglas G.; McKee, Amy S.; Rangel-Moreno, Javier; Martin, Allison K.; Getahun, Andrew; Maier, Lisa A.; Cambier, John C.; Tuder, Rubin M.; Fontenot, Andrew P.

doi:10.1172/jci.insight.125494

Cited by 18 publications

(20 citation statements)

References 51 publications

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“…Flow cytometry. AMs, BAL cells, and LDLN cells were analyzed by flow cytometry as described previously (2,11,12) and in Supplemental Methods. Cells were stained and washed with flow wash comprising DPBS containing 1% BSA (MilliporeSigma, A2153) and 0.1% NaN 3 (MilliporeSigma, SX0299).…”

Section: Methodsmentioning

confidence: 99%

“…Sterile particles with crystalline morphology (e.g., metal hydroxide salts, silica) promote cell stress and in some cases cell death in macrophages (1)(2)(3)(4)(5)(6). These factors drive lung inflammation and promote upregulation of costimulatory molecules on pulmonary conventional dendritic cells (cDCs) and thus regulate adaptive immune responses (1,5,(7)(8)(9)(10)(11). The release of IL-1α from dying AMs following crystalline particle inhalation is unique because other macrophage populations do not release IL-1α without a priming TLR signal (1,12).…”

Section: Introductionmentioning

confidence: 99%

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A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

et al. 2020

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

et al. 2020

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“…Our group recently demonstrated the importance of B cells in protecting the lung from beryllium oxide (BeO)-induced injury ( Table 1). Using a murine model of CBD that mimics the human disease, we established that activated follicular B cells are recruited to the lung after beryllium exposure and are organized into ectopic lymphoid aggregates (ELAs) (20). B cell depletion eradicated these ELAs and enhanced lung injury, indicating that B cells play an important protective role in BeO-induced lung injury (20).…”

Section: B Cell Involvement In Cbd and Sarcoidosismentioning

confidence: 99%

“…Using a murine model of CBD that mimics the human disease, we established that activated follicular B cells are recruited to the lung after beryllium exposure and are organized into ectopic lymphoid aggregates (ELAs) (20). B cell depletion eradicated these ELAs and enhanced lung injury, indicating that B cells play an important protective role in BeO-induced lung injury (20). In addition, BeO-induced B cell recruitment to the lung is dependent on MyD88 signaling (20).…”

Section: B Cell Involvement In Cbd and Sarcoidosismentioning

confidence: 99%

“…Certain MHCII molecules, primarily HLA-DPB1 in CBD and several HLA-DRB1 alleles in sarcoidosis, increase disease susceptibility (14)(15)(16)(17). Recently, there has also been evidence to suggest that B cells and antibody responses are involved in the pathogenesis of CBD and sarcoidosis (18)(19)(20). This review focuses on how different aspects of the immune system influence the progression of these diseases.…”

Section: Introductionmentioning

confidence: 99%

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Adaptive Immunity in Pulmonary Sarcoidosis and Chronic Beryllium Disease

2020

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Pulmonary sarcoidosis and chronic beryllium disease (CBD) are inflammatory granulomatous lung diseases defined by the presence of non-caseating granulomas in the lung. CBD results from beryllium exposure in the workplace, while the cause of sarcoidosis remains unknown. CBD and sarcoidosis are both immune-mediated diseases that involve Th1-polarized inflammation in the lung. Beryllium exposure induces trafficking of dendritic cells to the lung in a mechanism dependent on MyD88 and IL-1α. B cells are also recruited to the lung in a MyD88 dependent manner after beryllium exposure in order to protect the lung from beryllium-induced injury. Similar to most immune-mediated diseases, disease susceptibility in CBD and sarcoidosis is driven by the expression of certain MHCII molecules, primarily HLA-DPB1 in CBD and several HLA-DRB1 alleles in sarcoidosis. One of the defining features of both CBD and sarcoidosis is an infiltration of activated CD4+ T cells in the lung. CD4+ T cells in the bronchoalveolar lavage (BAL) of CBD and sarcoidosis patients are highly Th1 polarized, and there is a significant increase in inflammatory Th1 cytokines present in the BAL fluid. In sarcoidosis, there is also a significant population of Th17 cells in the lungs that is not present in CBD. Due to persistent antigen exposure and chronic inflammation in the lung, these activated CD4+ T cells often display either an exhausted or anergic phenotype. Evidence suggests that these T cells are responding to common antigens in the lung. In CBD there is an expansion of beryllium-responsive TRBV5.1+ TCRs expressed on pathogenic CD4+ T cells derived from the BAL of CBD patients that react with endogenous human peptides derived from the plexin A protein.In an acute form of sarcoidosis, there are expansions of specific TRAV12-1/TRBV2 T cell receptors expressed on BAL CD4+ T cells, indicating that these T cells are trafficking to and expanding in the lung in response to common antigens. The specificity of these pathogenic CD4+T cells in sarcoidosis are currently unknown.

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Beryllium

Rossman

Wambach²,

Ziegler‐Skylakakis

et al. 2023

Patty's Toxicology

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Beryllium, found in a variety of different forms, has become indispensable in modern high‐technology industries, especially aerospace. It has many attractive properties, including light weight, high strength, and heat resistance. Unfortunately, beryllium is associated with a number of toxic effects. Even under controlled conditions, beryllium metal, oxide, and alloys can cause chronic lung disease among individuals exposed to dust or fume. Identifying properties of different forms of beryllium are described in Section followed by sections which describe the properties and characteristics of beryllium. These include production and use, toxic effects, standards, and exposure assessment.

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Protective role of B cells in sterile particulate–induced lung injury

Cited by 18 publications

References 51 publications

A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

A role for TNF-α in alveolar macrophage damage-associated molecular pattern release

Adaptive Immunity in Pulmonary Sarcoidosis and Chronic Beryllium Disease

Beryllium

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