Although the function of the circulating immune cell compartment has been studied in detail for decades, limitations in terms of access and cell yields from peripheral tissues have restricted our understanding of tissue-based immunity, particularly in humans. Recent advances in high-throughput protein analyses, transcriptional profiling, and epigenetics have partially overcome these obstacles. Innate lymphoid cells (ILCs) are predominantly tissue-resident, and accumulating data indicate that they have significant tissue-specific functions. We summarize current knowledge of ILC phenotypes in various tissues in mice and humans, aiming to clarify ILC immunity in distinct anatomical locations.
BackgroundGroup 2 innate lymphoid cells (ILC2s) are involved in the initial phase of type 2 inflammation and can amplify allergic immune responses by orchestrating other type 2 immune cells. Prostaglandin (PG) E2 is a bioactive lipid that plays protective roles in the lung, particularly during allergic inflammation.ObjectiveWe set out to investigate how PGE2 regulates human ILC2 function.MethodsThe effects of PGE2 on human ILC2 proliferation and intracellular cytokine and transcription factor expression were assessed by means of flow cytometry. Cytokine production was measured by using ELISA, and real-time quantitative PCR was performed to detect PGE2 receptor expression.ResultsPGE2 inhibited GATA-3 expression, as well as production of the type 2 cytokines IL-5 and IL-13, from human tonsillar and blood ILC2s in response to stimulation with a combination of IL-25, IL-33, thymic stromal lymphopoietin, and IL-2. Furthermore, PGE2 downregulated the expression of IL-2 receptor α (CD25). In line with this observation, PGE2 decreased ILC2 proliferation. These effects were mediated by the combined action of E-type prostanoid receptor (EP) 2 and EP4 receptors, which were specifically expressed on ILC2s.ConclusionOur findings reveal that PGE2 limits ILC2 activation and propose that selective EP2 and EP4 receptor agonists might serve as a promising therapeutic approach in treating allergic diseases by suppressing ILC2 function.
Cross-reactive CD4 + T cells that recognize SARS-CoV-2 are more commonly detected in the peripheral blood of unexposed individuals compared to SARS-CoV-2-reactive CD8 + T cells. However, large numbers of memory CD8 + T cells reside in tissues, feasibly harboring localized SARS-CoV-2-specific immune responses. To test this idea, we performed a comprehensive functional and phenotypic analysis of virusspecific T cells in tonsils, a major lymphoid tissue site in the upper respiratory tract, and matched peripheral blood samples obtained from children and adults before the emergence of COVID-19. We found that SARS-CoV-2-specific memory CD4 + T cells could be found at similar frequencies in the tonsils and peripheral blood in unexposed individuals, whereas functional SARS-CoV-2-specific memory CD8 + T cells were almost only detectable in the tonsils. Tonsillar SARS-CoV-2-specific memory CD8 + T cells displayed a follicular homing and tissue-resident memory phenotype, similar to tonsillar Epstein-Barr virus-specific memory CD8 + T cells, but were functionally less potent than other virus-specific memory CD8 + T cell responses. The presence of pre-existing tissue-resident memory CD8 + T cells in unexposed individuals could potentially enable rapid sentinel immune responses against SARS-CoV-2.
Background: Group 2 innate lymphoid cells (ILC2s) play a key role in the initiation and maintenance of type 2 immune responses. The prostaglandin (PG) D 2 -chemoattractant receptor-homologous molecule expressed on T H 2 cells (CRTH2) receptor axis potently induces cytokine production and ILC2 migration.
In light of the beneficial targeting of IL-23/12 in patients with IBD, 1,25D appears as an interesting therapeutic agent that inhibits the IL-23 receptor pathway, providing a novel mechanism for how ILC3s could be manipulated to regulate intestinal inflammation.
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