Group-2 innate lymphoid cell-dependent regulation of tissue neutrophil migration by alternatively activated macrophage-secreted Ear11

Panova, Veera; Gogoi, Mayuri; Rodríguez-Rodríguez, Noé; Sivasubramaniam, Meera; Jolin, Helen E.; Heycock, Morgan W D; Walker, Jennifer; Rana, Batika M. J.; Drynan, Lesley; Hodskinson, M.R.G.; Pannell, Richard; King, Gareth; Wing, Mark; Easton, Andrew J.; Oedekoven, Caroline A.; Kent, David G.; Fallon, Padraic G.; Barlow, Jillian L.; McKenzie, Andrew N. J.

doi:10.1038/s41385-020-0298-2

Cited by 9 publications

(9 citation statements)

References 67 publications

(91 reference statements)

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“…As signature M2 macrophage genes, RELMα and Ym1/2 are reported to have equivalent expression patterns, but Ym1 can also promote RELMα expression ( 24 ). Ear11 is an eosinophil-associated ribonuclease that is secreted by M2 macrophages and promotes neutrophil chemotaxis ( 39 ). Consistent with IL-4 induced resident macrophage proliferation, genes associated with the cell cycle (Top2a, Cdc20, Kif20a, Ccnb2) were upregulated.…”

Section: Resultsmentioning

confidence: 99%

Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α

Kim

Lainez

et al. 2021

Front. Immunol.

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RELMα is a small, secreted protein expressed by type 2 cytokine-activated “M2” macrophages in helminth infection and allergy. At steady state and in response to type 2 cytokines, RELMα is highly expressed by peritoneal macrophages, however, its function in the serosal cavity is unclear. In this study, we generated RELMα TdTomato (Td) reporter/knockout (RαTd) mice and investigated RELMα function in IL-4 complex (IL-4c)-induced peritoneal inflammation. We first validated the RELMαTd/Td transgenic mice and showed that IL-4c injection led to the significant expansion of large peritoneal macrophages that expressed Td but not RELMα protein, while RELMα+/+ mice expressed RELMα and not Td. Functionally, RELMαTd/Td mice had increased IL-4 induced peritoneal macrophage responses and splenomegaly compared to RELMα+/+ mice. Gene expression analysis indicated that RELMαTd/Td peritoneal macrophages were more proliferative and activated than RELMα+/+ macrophages, with increased genes associated with T cell responses, growth factor and cytokine signaling, but decreased genes associated with differentiation and maintenance of myeloid cells. We tested the hypothesis that RαTd/Td macrophages drive aberrant T cell activation using peritoneal macrophage and T cell co-culture. There were no differences in CD4+ T cell effector responses when co-cultured with RELMα+/+ or RELMαTd/Td macrophages, however, RELMαTd/Td macrophages were impaired in their ability to sustain proliferation of FoxP3+ regulatory T cells (Treg). Supportive of the in vitro results, immunofluorescent staining of the spleens revealed significantly decreased FoxP3+ cells in the RELMαTd/Td spleens compared to RELMα+/+ spleens. Taken together, these studies identify a new RELMα regulatory pathway whereby RELMα-expressing macrophages directly sustain Treg proliferation to limit type 2 inflammatory responses.

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Section: Resultsmentioning

confidence: 99%

Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α

Kim

Lainez

et al. 2021

Front. Immunol.

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“…Such modulation of neutrophils has likely emerged in evolution together with the emergence of type 2 immune responses and the IL‐4 and IL‐13 genes 32 . Notably, IL‐4–/IL‐13–mediated modulation of neutrophils is also shaped by the concomitant production of other factors in the tissue microenvironment, including other cytokines, chemokines, and anti‐microbial proteins, such as chitinase‐like proteins, eosinophil‐associated ribonucleases, and eosinophil‐associated cationic proteins 31,33 …”

Section: Discussionmentioning

confidence: 99%

Patients with systemic sclerosis show phenotypic and functional defects in neutrophils

Impellizzieri

Egholm

Valaperti

et al. 2021

Allergy

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Background Systemic sclerosis (SSc) is a multiorgan autoimmune disease characterized by inflammation, vascular modification, and progressive fibrosis of the skin and several visceral organs. Innate and adaptive immune cells, including myeloid, B and T cells, are believed to be central to the pathogenesis of SSc. However, the role and functional state of neutrophil granulocytes (neutrophils) are ill‐defined in SSc. Methods We performed a prospective study of neutrophils freshly isolated from SSc patients and healthy donors (HD) by measuring in these neutrophils (i) functional cell surface markers, including CD16, CD62L, CD66b, CD66c, CXCR1, CXCR2, and CXCR4; (ii) cytokine‐activated intracellular signal transducer and activator of transcription (STAT) pathways, such as phosphorylated STAT3 (pSTAT3), pSTAT5, and pSTAT6; (iii) production of neutrophil extracellular traps (NET) and intracellular myeloperoxidase (MPO); and (iv) phagocytosis of bacteria by the neutrophils. Results Neutrophils of SSc patients expressed lower CD16 and CD62L and higher pSTAT3 and pSTAT6 compared to HD. Moreover, neutrophils of SSc patients lacked CXCR1 and CXCR2, the receptors responding to the potent neutrophil chemoattractant CXCL8. Neutrophils of SSc patients were also deficient in MPO levels, NET formation, and phagocytosis of bacteria. Conclusions Neutrophils of patients with SSc display several functional defects affecting cell migration, NET formation, and phagocytosis of bacteria.

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“…Another study reported that type 2 immunoregulatory neutrophil infiltration is influenced by mouse eosinophil associated ribonuclease 11, and is secreted by M2 macrophages downstream of ILC2s that are stimulated by IL-25 (111). Furthermore, neutrophils can promote type 2 immune response without aggravating inflammation (111).…”

Section: Pulmonary Viral and Fungal Infectionsmentioning

confidence: 99%

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

Zhu

Lü

2021

Mol Med Rep

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Type 2 innate lymphoid cells (ILC2s) are important innate immune cells that are involved in type 2 inflammation, in both mice and humans. ILC2s are stimulated by factors, including interleukin (IL)-33 and IL-25, and activated ILC2s secrete several cytokines that mediate type 2 immunity by inducing profound changes in physiology, including activation of alternative (M2) macrophages. M2 macrophages possess immune modulatory, phagocytic, tissue repair and remodeling properties, and can regulate ILC2s under infection. The present review summarizes the role of ILC2s as innate cells and M2 macrophages as anti-inflammatory cells, and discusses current literature on their important biological significance. The present review also highlights how the crosstalk between ILC2s and M2 macrophages contributes to lung development, induces pulmonary parasitic expulsion, exacerbates pulmonary viral and fungal infections and allergic airway diseases, and promotes the development of lung diseases, such as pulmonary fibrosis, chronic obstructive pulmonary disease and carcinoma of the lungs. Contents

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Group-2 innate lymphoid cell-dependent regulation of tissue neutrophil migration by alternatively activated macrophage-secreted Ear11

Cited by 9 publications

References 67 publications

Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α

Macrophage-Regulatory T Cell Interactions Promote Type 2 Immune Homeostasis Through Resistin-Like Molecule α

Patients with systemic sclerosis show phenotypic and functional defects in neutrophils

A crosstalk between type 2 innate lymphoid cells and alternative macrophages in lung development and lung diseases (Review)

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