Faculty Opinions recommendation of Anti-microbial Functions of Group 3 Innate Lymphoid Cells in Gut-Associated Lymphoid Tissues Are Regulated by G-Protein-Coupled Receptor 183.

G-protein-coupled receptor kinases (GRKs) mediate agonist-specific phosphorylation and desensitization of G-protein-coupled receptors. Previous studies have shown that several of these kinases are expressed in hematopoietic cells and that GRK expression is modulated during T-lymphocyte activation. Here, we analyzed the regulation of beta-adrenergic receptor kinase (betaARK) and GRK6 expression and activity in myelomonocytic and lymphoid cells. In the promyelocytic cell line HL- 60, GRK6 protein levels and activity rose twofold to fourfold over the course of treatment with agents that induce differentiation toward either the myeloid (dimethyl sulfoxide and retinoic acid) or monocytic [1alpha,25(OH)2-vitamin D3] lineage, whereas betaARK protein levels and activity were only slightly altered. In contrast, treatment with phorbol 12,13-myristic acetate (PMA) led to a reduction in steady-state levels and activity of both betaARK and GRK6. Treatment of human lymphocytes with several polyclonal activators (phytohemagglutinin, anti-CD3 antibody and interleukin-2) resulted in enhanced betaARK and GRK6 mRNA and protein levels and increased activity of both kinases. In contrast, PMA and calcium ionophore treatment significantly elevated GRK6 protein levels, while decreasing betaARK expression. These data demonstrate that betaARK and GRK6 expression are differentially regulated during myelomonocytic cell development and lymphocyte activation.

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Group 3 Innate Lymphoid Cells Program a Distinct Subset of IL-22BP-Producing Dendritic Cells Demarcating Solitary Intestinal Lymphoid Tissues

Immunity ◽

10.1016/j.immuni.2020.10.012 ◽

2020 ◽

Vol 53 (5) ◽

pp. 1015-1032.e8

Author(s):

Fabian Guendel ◽

Michael Kofoed-Branzk ◽

Konrad Gronke ◽

Caroline Tizian ◽

Mario Witkowski ◽

...

Keyword(s):

Dendritic Cells ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Lymphoid Tissues ◽

Distinct Subset ◽

Group 3

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Vasoactive intestinal peptide promotes host defense against enteric pathogens by modulating the recruitment of group 3 innate lymphoid cells

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.2106634118 ◽

2021 ◽

Vol 118 (41) ◽

pp. e2106634118

Author(s):

Hong Bing Yu ◽

Hyungjun Yang ◽

Joannie M. Allaire ◽

Caixia Ma ◽

Franziska A. Graef ◽

...

Keyword(s):

Vasoactive Intestinal Peptide ◽

Host Defense ◽

Innate Lymphoid Cells ◽

Lymphoid Cells ◽

Enteric Pathogens ◽

Lymphoid Tissues ◽

Homing Receptor ◽

Local Populations ◽

Ccr9 Expression ◽

Group 3

Group 3 innate lymphoid cells (ILC3s) control the formation of intestinal lymphoid tissues and play key roles in intestinal defense. They express neuropeptide vasoactive intestinal peptide (VIP) receptor 2 (VPAC2), through which VIP modulates their function, but whether VIP exerts other effects on ILC3 remains unclear. We show that VIP promotes ILC3 recruitment to the intestine through VPAC1 independent of the microbiota or adaptive immunity. VIP is also required for postnatal formation of lymphoid tissues as well as the maintenance of local populations of retinoic acid (RA)–producing dendritic cells, with RA up-regulating gut-homing receptor CCR9 expression by ILC3s. Correspondingly, mice deficient in VIP or VPAC1 suffer a paucity of intestinal ILC3s along with impaired production of the cytokine IL-22, rendering them highly susceptible to the enteric pathogen Citrobacter rodentium. This heightened susceptibility to C. rodentium infection was ameliorated by RA supplementation, adoptive transfer of ILC3s, or by recombinant IL-22. Thus, VIP regulates the recruitment of intestinal ILC3s and formation of postnatal intestinal lymphoid tissues, offering protection against enteric pathogens.

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Expression of the Open Reading Frame 74 (G-Protein-Coupled Receptor) Gene of Kaposi’s Sarcoma (KS)-Associated Herpesvirus: Implications for KS Pathogenesis

Journal of Virology ◽

10.1128/jvi.73.7.6006-6014.1999 ◽

1999 ◽

Vol 73 (7) ◽

pp. 6006-6014 ◽

Cited By ~ 111

Author(s):

Jessica R. Kirshner ◽

Katherine Staskus ◽

Ashley Haase ◽

Michael Lagunoff ◽

Don Ganem

Keyword(s):

G Protein ◽

Kaposi's Sarcoma ◽

Kaposi’S Sarcoma ◽

Lytic Replication ◽

Lymphoid Cells ◽

Lytic Cycle ◽

Viral Gene ◽

G Protein Coupled Receptor ◽

Nuclease Mapping ◽

G Protein Coupled

ABSTRACT Kaposi’s sarcoma (KS)-associated herpesvirus (KSHV) encodes a G-protein-coupled receptor (GCR) homolog. This protein is a potent, constitutively active signalling molecule that can influence both proliferation and angiogenesis when ectopically expressed in fibroblasts in vitro. Here we have examined the expression of the KSHV GCR gene in virus-infected lymphoid cells and in KS tumors. Our results show that in both situations the gene is expressed primarily during lytic replication; its transcription is unaffected by inhibition of viral DNA synthesis, indicating that it is expressed in the early phases of the lytic program. The major transcript bearing GCR sequences is bicistronic, harboring coding sequences for another viral gene, K14, at its 5′ end. Extensive searches for monocistronic GCR mRNAs using nuclease mapping and reverse transcription-PCR failed to detect such species. The 5′ end of K14/GCR mRNA maps to nucleotide (nt) 127848, and its poly(A) addition site maps to nt 130546; a 149-nt intron is present in the K14/GCR intergenic region. These results suggest that the KSHV GCR is translated by unconventional mechanisms involving either translational reinitiation, internal ribosomal entry, or leaky ribosomal scanning. The restriction of GCR expression to the lytic cycle has important implications for the potential role(s) of the GCR in KS pathogenesis.

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