Faculty Opinions recommendation of Dual role of YM1+ M2 macrophages in allergic lung inflammation.

We identify the tumor necrosis factor receptor superfamily 25 (TNFRSF25)/TNFSF15 pair as critical trigger for allergic lung inflammation, which is a cardinal feature of asthma. TNFRSF25 (TNFR25) signals are required to exert T helper cell 2 (Th2) effector function in Th2-polarized CD4 cells and co-stimulate interleukin (IL)-13 production by glycosphingolipid-activated NKT cells. In vivo, antibody blockade of TNFSF15 (TL1A), which is the ligand for TNFR25, inhibits lung inflammation and production of Th2 cytokines such as IL-13, even when administered days after airway antigen exposure. Similarly, blockade of TNFR25 by a dominant-negative (DN) transgene, DN TNFR25, confers resistance to lung inflammation in mice. Allergic lung inflammation–resistant, NKT-deficient mice become susceptible upon adoptive transfer of wild-type NKT cells, but not after transfer of DN TNFR25 transgenic NKT cells. The TNFR25/TL1A pair appears to provide an early signal for Th2 cytokine production in the lung, and therefore may be a drug target in attempts to attenuate lung inflammation in asthmatics.

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Dual Role of Hepatic Macrophages in the Establishment of the Echinococcus multilocularis Metacestode in Mice

Frontiers in Immunology ◽

10.3389/fimmu.2020.600635 ◽

2021 ◽

Vol 11 ◽

Author(s):

Hui Wang ◽

Chuan-Shan Zhang ◽

Bin-Bin Fang ◽

Jiao Hou ◽

Wen-Ding Li ◽

...

Keyword(s):

Echinococcus Multilocularis ◽

Liver Tissue ◽

Parasite Burden ◽

Dual Role ◽

M2 Macrophages ◽

Hepatic Macrophages ◽

M1 Phenotype ◽

Anti Inflammatory ◽

M2 Phenotype

Echinococcus multilocularis larvae, predominantly located in the liver, cause a tumor-like parasitic disease, alveolar echinococcosis (AE), that is characterized by increased infiltration of various immune cells, including macrophages, around the lesion that produces an “immunosuppressive” microenvironment, favoring its persistent infection. However, the role of hepatic macrophages in the host defense against E. multilocularis infection remains poorly defined. Using human liver tissues from patients with AE and a hepatic experimental mouse model of E. multilocularis, we investigated the phenotype and function of hepatic macrophages during the parasite infection. In the present study, we found that a large number of CD68+ macrophages accumulated around the metacestode lesion in the liver of human AE samples and that both S100A9+ proinflammatory (M1 phenotype) and CD163+ anti-inflammatory (M2 phenotype) macrophages were significantly higher in close liver tissue (CLT) than in distant liver tissue (DLT), whereas M2 macrophages represent the dominant macrophage population. Furthermore, E. multilocularis-infected mice exhibited a massive increase in macrophage (F4/80+) infiltration in the liver as early as day 5, and the infiltrated macrophages were mainly monocyte-derived macrophages (CD11bhi F4/80int MoMFs) that preferentially differentiated into the M1 phenotype (iNOS+) at the early stage of E. multilocularis infection and then polarized to anti-inflammatory macrophages of the M2 phenotype (CD206+) at the chronic stage of infection. We further showed that elimination of macrophages by treatment of mice with clodronate-liposomes before E. multilocularis infection impaired worm expulsion and was accompanied by a reduction in liver fibrosis, yielding a high parasite burden. These results suggest that hepatic macrophages may play a dual role in the establishment and development of E. multilocularis metacestodes in which early larvae clearance is promoted by M1 macrophages while persistent metacestode infection is favored by M2 macrophages.

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Cellular recruitment and cytokine generation in a rat model of allergic lung inflammation are differentially modulated by progesterone and estradiol

AJP Cell Physiology ◽

10.1152/ajpcell.00286.2006 ◽

2007 ◽

Vol 293 (3) ◽

pp. C1120-C1128 ◽

Cited By ~ 45

Author(s):

Ana Paula Ligeiro de Oliveira ◽

Helori Vanni Domingos ◽

Gabriela Cavriani ◽

Amilcar Sabino Damazo ◽

Adriana Lino dos Santos Franco ◽

...

Keyword(s):

Lung Inflammation ◽

Estradiol Treatment ◽

Cell Recruitment ◽

Ovx Rats ◽

Allergic Lung Inflammation ◽

Tnf Α ◽

Cellular Recruitment ◽

Additional Reduction

We evaluated the role of estradiol and progesterone in allergic lung inflammation. Rats were ovariectomized (Ovx) and, 7 days later, were sensitized with ovalbumin (OA) and challenged after 2 wk with inhaled OA; experiments were performed 1 day thereafter. Ovx-allergic rats showed reduced cell recruitment into the bronchoalveolar lavage (BAL) fluid relative to sham-Ovx allergic rats, as was observed in intact allergic rats treated with ICI-182,780. Estradiol increased the number of cells in the BAL of Ovx-allergic rats, whereas progesterone induced an additional reduction. Cells of BAL and bone marrow (BM) of Ovx-allergic rats released elevated amounts of IL-10 and reduced IL-1β and TNF-α. BM cells of Ovx-allergic rats released increased amounts of IL-10 and lower amounts of IL-4. Estradiol treatment of Ovx-allergic rats decreased the release of IL-10 but increased that of IL-4 by BM cells. Estradiol also caused an increased release of IL-1β and TNF-α by BAL cells. Progesterone significantly increased the release of IL-10, IL-1β, and TNF-α by BAL cells and augmented that of IL-4 by BM cells. Degranulation of bronchial mast cells from Ovx rats was reduced after in vitro challenge, an effect reverted by estradiol but not by progesterone. We suggest that the serum estradiol-to-progesterone ratio might drive cellular recruitment, modulating the pulmonary allergy and profile of release of anti-inflammatory or inflammatory cytokines. The existence of such dual hormonal effects suggests that the hormone therapy of asthmatic postmenopausal women and of those suffering of premenstrual asthma should take into account the possibility of worsening the pulmonary conditions.

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Update on the role of prostaglandins in allergic lung inflammation: Separating friends from foes, harder than you might think

Journal of Allergy and Clinical Immunology ◽

10.1016/j.jaci.2005.12.1314 ◽

2006 ◽

Vol 117 (5) ◽

pp. 1036-1039 ◽

Cited By ~ 33

Author(s):

Martin L. Moore ◽

R. Stokes Peebles

Keyword(s):

Lung Inflammation ◽

Allergic Lung Inflammation

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The Role of α 4 (CD49d) and β 2 (CD18) Integrins in Eosinophil and Neutrophil Migration to Allergic Lung Inflammation in the Brown Norway Rat

American Journal of Respiratory Cell and Molecular Biology ◽

10.1165/ajrcmb.20.3.3207 ◽

1999 ◽

Vol 20 (3) ◽

pp. 448-457 ◽

Cited By ~ 30

Author(s):

Thorsten Schneider ◽

Thomas B. Issekutz ◽

Andrew C. Issekutz

Keyword(s):

Lung Inflammation ◽

Neutrophil Migration ◽

Brown Norway ◽

Norway Rat ◽

Allergic Lung Inflammation ◽

Brown Norway Rat

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Dual role of interleukin-10 in the regulation of respiratory syncitial virus (RSV)-induced lung inflammation

Clinical & Experimental Immunology ◽

10.1111/cei.12059 ◽

2013 ◽

Vol 172 (2) ◽

pp. 263-279 ◽

Cited By ~ 26

Author(s):

L. Sun ◽

T. T. Cornell ◽

A. LeVine ◽

A. A. Berlin ◽

V. Hinkovska-Galcheva ◽

...

Keyword(s):

Lung Inflammation ◽

Interleukin 10 ◽

Dual Role

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Reduced allergic lung inflammation and airway responsiveness in mice lacking the cytoskeletal protein gelsolin

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00065.2020 ◽

2020 ◽

Vol 319 (5) ◽

pp. L833-L842

Author(s):

Maya Mikami ◽

Gene T. Yocum ◽

Nicola M. Heller ◽

Charles W. Emala

Keyword(s):

Airway Inflammation ◽

Lung Inflammation ◽

Ex Vivo ◽

Cell Types ◽

Asthma Severity ◽

Wild Type ◽

Allergic Lung Inflammation ◽

Actin Capping

Airway smooth muscle hyperresponsiveness associated with chronic airway inflammation leads to the typical symptoms of asthma including bronchoconstriction and wheezing. Asthma severity is associated with airway inflammation; therefore, reducing airway inflammation is an important therapeutic target. Gelsolin is an actin capping and severing protein that has been reported to be involved in modulation of the inflammatory response. Using mice genetically lacking gelsolin, we evaluated the role of gelsolin in the establishment of house dust mite (HDM) antigen-induced allergic lung inflammation. The genetic absence of gelsolin was found to be protective against HDM sensitization, resulting in reduced lung inflammation, inflammatory cytokines, and Muc5AC protein in bronchoalveolar lavage (BAL) fluid. The number of eosinophils, lymphocytes, and interstitial macrophages in the BAL were increased after HDM sensitization in wild-type mice but were attenuated in gelsolin-null mice. The observed attenuation of inflammation may be partly due to delayed migration of immune cells, because the reduced eosinophils in the BALs from gelsolin-null mice compared with controls occurred despite similar amounts of the chemoattractant eotaxin. Splenic T cells demonstrated similar proliferation rates, but ex vivo alveolar macrophage migration was delayed in gelsolin-null mice. In vivo, the reduced lung inflammation after HDM sensitization in gelsolin-null mice was associated with significantly diminished airway resistance to inhaled methacholine compared with HDM-treated wild-type mice. Our results suggest that modulation of gelsolin expression or function in selective inflammatory cell types that modulate allergic lung inflammation could be a therapeutic approach for asthma.

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