scholarly journals The first functional characterization of ancient interleukin-15-like (IL-15L) reveals shared and distinct functions of the IL-2, -15 and -15L family cytokines

2019 ◽  
Author(s):  
Takuya Yamaguchi ◽  
Axel Karger ◽  
Markus Keller ◽  
Eakapol Wangkahart ◽  
Tiehui Wang ◽  
...  
Keyword(s):  
Receptor Gene ◽  
Functional Characterization ◽  
Interferon Γ ◽  
Lymphoid Cells ◽  
Molecular Evidence ◽  
Induced Expression ◽  
Mucosal Tissues ◽  
Receptor Chain ◽  
Interleukin 15

AbstractThe ancient cytokine interleukin 15-like (IL-15L) was lost in humans and mice but not throughout mammals. This is the first study to describe IL-15L functions, namely in the fish rainbow trout. Fish have only one α-chain receptor geneIL-15Rα, whereas in mammalian evolution this gene duplicated and evolved intoIL-15RαplusIL-2Rα. Trout IL-2, IL-15 and IL-15L all could bind IL-15Rα and were able to induce phosphorylation of transcription factor STAT5. Reminiscent of the mammalian situation, trout IL-15 was more dependent on “intrans” presentation by IL-15Rα than IL-2. However, whereas trout IL-15 could also function as a free cytokine as known for mammalian IL-15, trout IL-15L function showed a total dependency on intranspresentation by IL-15Rα. Trout lymphocytes from the mucosal tissues gill and intestine were sensitive to IL-15, but refractory to IL-2 and IL-15L, which is reminiscent of sensitivities to IL-15 in mammals. Distinguishing engagement of the IL-2Rα/IL-15Rα receptor chain may explain why IL-2 and IL-15 were selected in evolution as major growth factors for regulatory T cells and lymphocytes in mucosal tissues, respectively. Trout IL-15L efficiently induced expression ofIL-4andIL-13homologues in CD4-CD8-IgM-splenocytes, and we speculate that the responsive cells within that population were type 2 innate lymphoid cells (ILC2). In contrast, trout IL-15 efficiently induced expression ofinterferon γandperforinin CD4-CD8-IgM-splenocytes, and we speculate that in this case the responsive cells were natural killer (NK) cells. In fish, in apparent absence of IL-25, IL-33 and TSLP, primitive IL-15L may have an important role early in the type 2 immunity cytokine cascade. Among trout thymocytes, only CD4-CD8-thymocytes were sensitive to IL-15L, and different than in mammals the CD4+CD8+thymocytes were quite sensitive to IL-2. In addition, the present study provides (i) the first molecular evidence for inter-species cytokine with receptor chain interaction across fish-mammal borders, and (ii) suggestive evidence for a tendency of IL-2/15/15L cytokines to form homodimers as an ancient family trait. This is the first comprehensive study on IL-2/15/15L functions in fish and it provides important insights into the evolution of this cytokine family.

scholarly journals Pulmonary environmental cues drive group 2 innate lymphoid cell dynamics in mice and humans

2019 ◽  
Vol 4 (36) ◽  
pp. eaav7638 ◽  
Author(s):  
Franz Puttur ◽  
Laura Denney ◽  
Lisa G. Gregory ◽  
Juho Vuononvirta ◽  
Robert Oliver ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Lymphoid Cells ◽  
Perivascular Spaces ◽  
Cell Dynamics ◽  
Mucosal Tissues ◽  
Migratory Patterns ◽  
Group 2 ◽  
Environmental Exploration ◽  
Type 2 Inflammation

Group 2 innate lymphoid cells (ILC2s) are enriched in mucosal tissues (e.g., lung) and respond to epithelial cell–derived cytokines initiating type 2 inflammation. During inflammation, ILC2 numbers are increased in the lung. However, the mechanisms controlling ILC2 trafficking and motility within inflamed lungs remain unclear and are crucial for understanding ILC2 function in pulmonary immunity. Using several approaches, including lung intravital microscopy, we demonstrate that pulmonary ILC2s are highly dynamic, exhibit amoeboid-like movement, and aggregate in the lung peribronchial and perivascular spaces. They express distinct chemokine receptors, including CCR8, and actively home to CCL8 deposits located around the airway epithelium. Within lung tissue, ILC2s were particularly motile in extracellular matrix–enriched regions. We show that collagen-I drives ILC2 to markedly change their morphology by remodeling their actin cytoskeleton to promote environmental exploration critical for regulating eosinophilic inflammation. Our study provides previously unappreciated insights into ILC2 migratory patterns during inflammation and highlights the importance of environmental guidance cues in the lung in controlling ILC2 dynamics.

scholarly journals The Fate of Activated Group 2 Innate Lymphoid Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura Mathä ◽  
Itziar Martinez-Gonzalez ◽  
Catherine A. Steer ◽  
Fumio Takei
Keyword(s):  
Stromal Cells ◽  
Inflammatory Diseases ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
First Line ◽  
The Past ◽  
Mucosal Tissues ◽  
Group 2 ◽  
Type 2 Inflammation

Group 2 innate lymphoid cells (ILC2s) reside in both mucosal and non-mucosal tissues and play critical roles in the first line of defense against parasites and irritants such as allergens. Upon activation by cytokines released from epithelial and stromal cells during tissue damage or stimulation, ILC2s produce copious amounts of IL-5 and IL-13, leading to type 2 inflammation. Over the past 10 years, ILC2 involvement in a variety of human diseases has been unveiled. However, questions remain as to the fate of ILC2s after activation and how that might impact their role in chronic inflammatory diseases such as asthma and fibrosis. Here, we review studies that have revealed novel properties of post-activation ILC2s including the generation of immunological memory, exhausted-like phenotype, transdifferentiation and activation-induced migration.

A pro-inflammatory role of type 2 innate lymphoid cells in murine immune-mediated hepatitis

2015 ◽  
Vol 53 (12) ◽  
Author(s):  
K Karimi ◽  
K Neumann ◽  
J Meiners ◽  
R Voetlause ◽  
W Dammermann ◽  
...  
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Immune Mediated

1886-P: Hepatic Type 2 Innate Lymphoid Cells Suppress Gluconeogenesis via the IL-33/GATA3/IL-13 Axis

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1886-P
Author(s):  
MASANORI FUJIMOTO ◽  
KOUTARO YOKOTE ◽  
TOMOAKI TANAKA
Keyword(s):  
Innate Lymphoid Cells ◽  
Lymphoid Cells
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