PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

Oyesola, Oyebola O.; Shanahan, Michael T.; Kanke, Matt; Mooney, Bridget; Webb, Lauren M.; Smita, Shuchi; Matheson, Macy K.; Campioli, Pamela; Pham, Duc Hung; Früh, Simon; McGinty, John W.; Churchill, Madeline J.; Cahoon, Jordan L.; Sundaravaradan, Pavithra; Flitter, Becca A.; Mouli, Karthik; Nadjsombati, Marija S.; Kamynina, Elena; Peng, Seth A.; Cubitt, Rebecca L.; Gronert, Karsten; Lord, James D.; Rauch, Isabella; Moltke, Jakob von; Sethupathy, Praveen; Wojno, Elia D. Tait

doi:10.1084/jem.20202178

Cited by 41 publications

(50 citation statements)

References 78 publications

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“…The traditional model of DC maturation involves TLR signaling on the DC ( Dalod et al, 2014 ). IL-1R ( Pang et al, 2013 ) or IL-18R ( Li et al, 2004 ) on these cells might also trigger maturation, though further investigation is needed to understand how IL-1β, IL-18, or other inflammatory signals, such as eicosanoids ( McDougal et al, 2021 ; Oyesola et al, 2021 ; Rauch et al, 2017 ), downstream of inflammasome activation might drive maturation of DCs that have acquired IEC-derived antigen.…”

Section: Discussionmentioning

confidence: 99%

Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

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Doyle

Rauch

et al. 2021

eLife

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The innate immune system detects pathogens and initiates adaptive immune responses. Inflammasomes are central components of the innate immune system, but whether inflammasomes provide sufficient signals to activate adaptive immunity is unclear. In intestinal epithelial cells (IECs), inflammasomes activate a lytic form of cell death called pyroptosis, leading to epithelial cell expulsion and the release of cytokines. Here we employed a genetic system to show that simultaneous antigen expression and inflammasome activation specifically in IECs is sufficient to activate CD8+ T cells. By genetic elimination of direct T cell priming by IECs, we found that IEC-derived antigens are cross-presented to CD8+ T cells. However, cross-presentation of IEC-derived antigen to CD8+ T cells only partially depended on IEC pyroptosis. In the absence of inflammasome activation, cross-priming of CD8+ T cells required Batf3+ dendritic cells (cDC1), whereas cross-priming in the presence of pyroptosis required a Zbtb26+ but Batf3-independent cDC population. These data suggest the existence of parallel pyroptosis-dependent and pyroptosis-independent pathways for cross-presentation of IEC-derived antigens.

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Section: Discussionmentioning

confidence: 99%

Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

Deets

Doyle

Rauch

et al. 2021

eLife

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“…Regardless of whether CRTH2 is important for murine ILC2 regulation or not, a common feature in both species is that one of the main sources of PGD2 are mast cells, providing a potential direct interaction between those two cell types. Other sources of PGD2 such as Tuft cells have been characterized in the small intestine in helminth infection ( 146 ) or dendritic cells in skin ( 147 ). Finally, the interesting observation that ILC2s can produce PGD2 themselves also hints to a possible autocrine function of this signal on ILC2s that requires further characterization.…”

Section: Lipid Mediator Receptorsmentioning

confidence: 99%

Tissue-Specific Molecular Markers and Heterogeneity in Type 2 Innate Lymphoid Cells

2021

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Innate lymphoid cells (ILCs) are the most recently described group of lymphoid subpopulations. These tissue-resident cells display a heterogeneity resembling that observed on different groups of T cells, hence their categorization as cytotoxic NK cells and helper ILCs type 1, 2 and 3. Each one of these groups is highly diverse and expresses different markers in a context-dependent manner. Type 2 innate lymphoid cells (ILC2s) are activated in response to helminth parasites and regulate the immune response. They are involved in the etiology of diseases associated with allergic responses as well as in the maintenance of tissue homeostasis. Markers associated with their identification differ depending on the tissue and model used, making the study and understanding of these cells a cumbersome task. This review compiles evidence for the heterogeneity of ILC2s as well as discussion and analyses of molecular markers associated with their identity, function, tissue-dependent expression, and how these markers contribute to the interaction of ILC2s with specific microenvironments to maintain homeostasis or respond to pathogenic challenges.

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“…Of note, mast cells are likely not the only source of PGD2. Although studied not specifically in the skin, ILC2s and epithelial cells have also been found to produce PGD2 (35)(36)(37).…”

Section: Ilcs In the Skinmentioning

confidence: 99%

Innate Lymphoid Cells in Skin Homeostasis and Malignancy

Wagner

Koyasu

2021

Front. Immunol.

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Innate lymphoid cells (ILCs) are mostly tissue resident lymphocytes that are preferentially enriched in barrier tissues such as the skin. Although they lack the expression of somatically rearranged antigen receptors present on T and B cells, ILCs partake in multiple immune pathways by regulating tissue inflammation and potentiating adaptive immunity. Emerging evidence indicates that ILCs play a critical role in the control of melanoma, a type of skin malignancy thought to trigger immunity mediated mainly by adaptive immune responses. Here, we compile our current understanding of ILCs with regard to their role as the first line of defence against melanoma development and progression. We also discuss areas that merit further investigation. We envisage that the possibility to harness therapeutic potential of ILCs might benefit patients suffering from skin malignancies such as melanoma.

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PGD2 and CRTH2 counteract Type 2 cytokine–elicited intestinal epithelial responses during helminth infection

Cited by 41 publications

References 78 publications

Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

Inflammasome activation leads to cDC1-independent cross-priming of CD8 T cells by epithelial cell-derived antigen

Tissue-Specific Molecular Markers and Heterogeneity in Type 2 Innate Lymphoid Cells

Innate Lymphoid Cells in Skin Homeostasis and Malignancy

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