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Macrophage-regulatory T cell interactions promote type 2 immune homeostasis through Resistin-like molecule α

ABSTRACT: Macrophage-regulatory T cell interactions promote type 2 immune homeostasis through Resistin-like molecule α

PROVIDER: PRJNA730719 | ENA |

REPOSITORIES: ENA

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

Project description: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.

| S-EPMC8327085 | biostudies-literature

Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

Project description:Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

| PRJNA428363 | ENA

Resistin-like molecule α provides vitamin A-dependent antimicrobial protection of the skin

Project description:The skin is the human body’s largest organ and is in contact with a diverse community of microorganisms that includes both resident and pathogenic bacteria. Skin immune defenses include the production of antimicrobial proteins that kill bacteria directly. However, we still have an incomplete understanding of how skin antimicrobial proteins promote homeostasis with resident bacterial communities and limit infection. Here, we show that resistin-like molecule α (RELMα) is an antibacterial protein that is produced by keratinocytes and sebocytes in the mouse skin. RELMα expression was induced in mouse skin by resident and pathogenic skin bacteria and was bactericidal for several bacterial species found on the skin, including Streptococcus pyogenes. Mice lacking RELMα had altered resident skin bacterial communities and were more susceptible to bacterial infection, indicating that RELMα controls bacterial colonization of the skin. RELMα expression required dietary vitamin A and could be induced by therapeutic retinoids that protected against bacterial infection in a RELMα-dependent manner. Resistin, another member of the RELM family, was expressed in human skin, required retinoids for expression, and killed skin bacteria, indicating a conserved function for RELM proteins in skin innate immunity. Our findings thus identify members of the RELM family as antibacterial proteins that provide vitamin A-dependent antimicrobial protection of the skin, and provide insight into why skin immunity requires adequate dietary vitamin A.

2019-04-30 | GSE108718 | GEO

Macrophage-regulatory T cell interactions promote type 2 immune homeostasis through Resistin-like molecule α

Project description:RELMα is a small, secreted protein expressed by T helper type 2 (Th2) cytokine activated “M2” macrophages in helminth infection and allergy. At steady state and in response to Th2 cytokines, RELMα is highly expressed by peritoneal macrophages. We generated RELMα TdTomato (Td) reporter/knockout (RΕLMαTd/Td) mice. RELMαTd/Td mice had increased IL-4 induced peritoneal macrophage responses and splenomegaly compared to RELMα+/+ mice. Nanostring data indicated that RELMαTd/Td peritoneal macrophages were more proliferative and activated than RELMα+/+ macrophages, with increased genes associated with T cell response, growth factor and cytokine signaling, but decreased genes associated with differentiation and maintenance of myeloid cells.This studies identify a new RELMα regulatory pathway whereby RELMα-expressing macrophages directly sustain Treg proliferation to limit Th2 inflammatory responses.

2021-07-09 | GSE174606 | GEO

Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis

Project description:Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis

| PRJNA973104 | ENA

Investigating the role of cell adhesion molecule alpha-catenin during islet development

Project description:Investigating the role of cell adhesion molecule alpha-catenin during islet development

| PRJNA788481 | ENA

Expression Homeostasis during DNA Replication [DNA/ChIP-seq data alpha-factor]

Project description:Expression Homeostasis during DNA Replication [DNA/ChIP-seq data alpha-factor]

| PRJEB12575 | ENA

Protein Kinase A (PKAc alpha ) regulates gastric homeostasis and preneoplastic lesions

Project description:Protein Kinase A (PKAc alpha ) regulates gastric homeostasis and preneoplastic lesions

| PRJNA803995 | ENA

An estrogen receptor α-derived peptide improves glucose homeostasis during obesity

Project description:An estrogen receptor α-derived peptide improves glucose homeostasis during obesity

| PRJNA1093463 | ENA

Multiplex Chromatin Interactions with Single Molecule Precision

Project description:Multiplex Chromatin Interactions with Single Molecule Precision

| PRJNA430678 | ENA

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