Lymph node–resident dendritic cells drive T
            <sub>H</sub>
            2 cell development involving MARCH1

Castellanos, Carlos A.; Ren, Xin; Gonzalez, Steven Lomeli; Li, Hong Kun; Schroeder, Andrew; Liang, Hong; Laidlaw, Brian J.; Hu, Donglei; Mak, Angel C. Y.; Eng, Celeste; Rodríguez‐Santana, José; LeNoir, Michael A.; Qi, Yan; Celedón, Juan C.; Burchard, Esteban G.; Zamvil, Scott S.; Ishido, Satoshi; Locksley, Richard M.; Cyster, Jason G.; Huang, Xiaozhu; Shin, Jeoung Sook

doi:10.1126/sciimmunol.abh0707

Cited by 14 publications

(9 citation statements)

References 76 publications

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“…Collectively, our present findings suggest that some, if not much, of the sensitization and progression of allergies may occur systemically through the presentation of allergens by GMiDCs in the spleen. Further works are required to investigate the specific roles of GMiDCs in various tissues and LNs considering that the resDCs in the LNs were recently shown to drive Th2 polarization (70).…”

Section: Discussionmentioning

confidence: 99%

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

et al. 2022

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Dendritic cells (DCs) are key antigen-presenting cells that prime naive T cells and initiate adaptive immunity. Although the genetic deficiency and transgenic overexpression of granulocyte macrophage-colony stimulating factor (GM-CSF) signaling were reported to influence the homeostasis of DCs, the in vivo development of DC subsets following injection of GM-CSF has not been analyzed in detail. Among the treatment of mice with different hematopoietic cytokines, only GM-CSF generates a distinct subset of XCR1-33D1- DCs which make up the majority of DCs in the spleen after three daily injections. These GM-CSF-induced DCs (GMiDCs) are distinguished from classical DCs (cDCs) in the spleen by their expression of CD115 and CD301b and by their superior ability to present blood-borne antigen and thus to stimulate CD4+ T cells. Unlike cDCs in the spleen, GMiDCs are exceptionally effective to polarize and expand T helper type 2 (Th2) cells and able to induce allergic sensitization in response to blood-borne antigen. Single-cell RNA sequencing analysis and adoptive cell transfer assay reveal the sequential differentiation of classical monocytes into pre-GMiDCs and GMiDCs. Interestingly, mixed bone marrow chimeric mice of Csf2rb+/+ and Csf2rb-/- demonstrate that the generation of GMiDCs necessitates the cis expression of GM-CSF receptor. Besides the spleen, GMiDCs are generated in the CCR7-independent resident DCs of the LNs and in some peripheral tissues with GM-CSF treatment. Also, small but significant numbers of GMiDCs are generated in the spleen and other tissues during chronic allergic inflammation. Collectively, our present study identifies a splenic subset of CD115hiCD301b+ GMiDCs that possess a strong capacity to promote Th2 polarization and allergic sensitization against blood-borne antigen.

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Section: Discussionmentioning

confidence: 99%

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

et al. 2022

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“…The expression of MARCH1 in DCs plays an important role in Th2 polarization 15 , and can be up regulated by stressful events 16 . Thus, based on the results in Figure 5 , we examined the role of MARCH1 in compromising the immune therapeutic efficacy of SIT.…”

Section: Resultsmentioning

confidence: 99%

“…MARCH1 is an E3 ligase and can help target protein breakdown 17 . Recent studies have also shown that MARCH1 interferes with immune regulatory functions, particularly by favoring Th2 polarization 15 . MARCH1 expression can disrupt DC homeostasis and disturb immune regulatory activities 15 .…”

Section: Discussionmentioning

confidence: 99%

Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy

Liu²,

Xiao³

et al. 2022

Theranostics

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Background:The therapeutic efficacy of allergen specific immunotherapy (SIT) is recognized, but needs improved. Psychological stress influences the immune system's function. The objective of this study is to elucidate the effects of psychological stress on compromising the effectiveness of SIT. Methods: A murine model with the airway allergic disorder (AAD) was established. Mice were treated with SIT with or without restraint stress (Rs). Results: Rs was found to significantly hamper the efficacy of SIT in mice with AAD. Induction of IL-10 + dendritic cells and type 1 regulatory T cells were reduced by Rs in the airway tissues. Rs-induced cortisol release subverted immune tolerance generation. Expression of MARCH1 was elevated in dendritic cells of the allergic lesion sites. The Rs-induced MARCH1 mediated the immune impairment in AAD mice. Genetic ablation of MARCH1 in dendritic cells efficiently blocked the Rs-compromised the therapeutic efficacy of SIT. Conclusion: Rs can increase the expression of MARCH1 in DCs of the allergic lesion sites. MARCH1 interferes with the immune regulatory properties in DCs, and impairs the immune regulatory capacity. Blocking MARCH1 can counteract the Rs-affected SIT efficacy.

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“…The discrepancy of this study from ours may represent inherent differences in the mouse models of asthma. We did not address the distinct or redundant contribution of MARCH1 among myeloid APCs (i.e., DC or macrophage subsets), although our previous work showed that MARCH1 in the lymph node resident DCs plays a critical role for Th2 cell priming and sequential Th2 cell responses (26). This previous work did not exclude a role for MARCH1 among lung APCs (i.e., DC or macrophage subsets), which we have shown in this study could also contribute to effectuation of a Th2 cell response.…”

Section: Discussionmentioning

confidence: 99%

MARCH1 Controls an Exhaustion-like Program of Effector CD4+ T Cells Promoting Allergic Airway Inflammation

et al. 2022

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Persistent antigenic signaling leads to T cell exhaustion, a dysfunctional state arising in many chronic infections and cancers. Little is known concerning mechanisms limiting exhaustion in immune-stimulatory diseases such as asthma. We report that membraneassociated RING-CH1 (MARCH1), the ubiquitin ligase that mediates surface turnover of MHC class II (MHCII) and CD86 in professional APCs, plays an essential role in restraining an exhaustion-like program of effector CD4 + T cells in a mouse model of asthma. Mice lacking MARCH1 or the ubiquitin acceptor sites of MHCII and CD86 exhibited increased MHCII and CD86 surface expression on lung APCs, and this increase promoted enhanced expression of immune-inhibitory receptors by effector CD4 + T cells and inhibited their proliferation. Remarkably, ablation of MARCH1 in mice with established asthma reduced airway infiltration of eosinophils and Th2 cells. Thus, MARCH1 controls an exhaustion-like program of effector CD4 + T cells during allergic airway inflammation and may serve as a therapeutic target for asthma. ImmunoHorizons, 2022, 6: 684-692.

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Lymph node–resident dendritic cells drive T _H 2 cell development involving MARCH1

Abstract: Type 2 immune development depends on MARCH1-mediated turnover of MHCII and CD86 by lymph node–resident dendritic cells.

Cited by 14 publications

References 76 publications

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy

MARCH1 Controls an Exhaustion-like Program of Effector CD4+ T Cells Promoting Allergic Airway Inflammation

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Lymph node–resident dendritic cells drive T H 2 cell development involving MARCH1

Abstract: Type 2 immune development depends on MARCH1-mediated turnover of MHCII and CD86 by lymph node–resident dendritic cells.

Cited by 14 publications

References 76 publications

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

Granulocyte Macrophage-Colony Stimulating Factor Produces a Splenic Subset of Monocyte-Derived Dendritic Cells That Efficiently Polarize T Helper Type 2 Cells in Response to Blood-Borne Antigen

Targeting psychological stress-steroid-MARCH1 signaling pathway promotes the efficacy of specific allergen immunotherapy

MARCH1 Controls an Exhaustion-like Program of Effector CD4+ T Cells Promoting Allergic Airway Inflammation

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Lymph node–resident dendritic cells drive T _H 2 cell development involving MARCH1