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Abstract: Invariant NKT (iNKT) cells are a distinct subset of T cells that exert Janus‐like functions in vivo by producing IFN‐γ and IL‐4. Sodium chloride modulates the functions of various immune cells, including conventional CD4+ T cells and macrophages. However, it is not known whether sodium chloride affects iNKT cell function, so we addressed this issue. Sodium chloride inhibited IFN‐γ, but not IL‐4, production by iNKT cells upon TCR or TCR‐independent (IL‐12 and IL‐18) stimulation in a dose‐dependent manner. Consistently, sodium chloride reduced the expression level of tbx21, but not gata‐3, in iNKT cells stimulated with TCR engagement or IL‐12 + IL‐18. Sodium chloride increased phosphorylated p38 expression in iNKT cells and inhibitors of p38, NFAT5, SGK1, and TCF‐1 restored IFN‐γ production by iNKT cells stimulated with sodium chloride and TCR engagement. Furthermore, adoptive transfer of iNKT cells pretreated with sodium chloride restored antibody‐induced joint inflammation to a lesser extent than for untreated iNKT cells in Jα18 knockout mice. These findings suggest that sodium chloride inhibits IFN‐γ production by iNKT cells in TCR‐dependent and TCR‐independent manners, which is dependent on p38, NFAT5, SGK1, and TCF‐1. These findings highlight the functional role of sodium chloride in iNKT cell‐mediated inflammatory diseases. [ABSTRACT FROM AUTHOR]

The intricate role of innate type-2 cytokines in immune responses is increasingly acknowledged for its dual nature, encompassing both protective and pathogenic dimensions. Ranging from defense against parasitic infections to contributing to inflammatory diseases like asthma, fibrosis, and obesity, these cytokines intricately engage with various innate immune cells. This review meticulously explores the cellular origins of innate type-2 cytokines and their intricate interactions, shedding light on factors that amplify the innate type-2 response, including TSLP, IL-25, and IL-33. Recent advancements in therapeutic strategies, specifically the utilization of biologics targeting pivotal cytokines (IL-4, IL-5, and IL-13), are discussed, offering insights into both challenges and opportunities. Acknowledging the pivotal role of innate type-2 cytokines in orchestrating immune responses positions them as promising therapeutic targets. The evolving landscape of research and development in this field not only propels immunological knowledge forward but also holds the promise of more effective treatments in the future., Competing Interests: Conflict of Interest: The authors declare no potential conflicts of interest., (Copyright © 2024. The Korean Association of Immunologists.)

To date, no study has demonstrated that soluble Fas ligand (sFasL)-mediated inflammation is regulated via interaction with Fas in vivo. We found that FasL interacts specifically with tumor necrosis factor receptor superfamily (TNFRSF)10B, also known as death receptor (DR)5. Autoantibody-induced arthritis (AIA) was attenuated in FasL ( Fasl gld/gld )- and soluble FasL ( Fasl Δs/Δs )-deficient mice, but not in Fas ( Fas lpr/lpr and Fas -/- )- or membrane FasL ( Fasl Δm/Δm )-deficient mice, suggesting sFasL promotes inflammation by binding to a Fas-independent receptor. Affinity purification mass spectrometry analysis using human (h) fibroblast-like synovial cells (FLSCs) identified DR5 as one of several proteins that could be the elusive Fas-independent FasL receptor. Subsequent cellular and biochemical analyses revealed that DR5 interacted specifically with recombinant FasL-Fc protein, although the strength of this interaction was approximately 60-fold lower than the affinity between TRAIL and DR5. A microarray assay using joint tissues from mice with arthritis implied that the chemokine CX3CL1 may play an important downstream role of the interaction. The interaction enhanced Cx3cl1 transcription and increased sCX3CL1 production in FLSCs, possibly in an NF-κB-dependent manner. Moreover, the sFasL-DR5 interaction-mediated CX3CL1-CX3CR1 axis initiated and amplified inflammation by enhancing inflammatory cell influx and aggravating inflammation via secondary chemokine production. Blockade of FasL or CX3CR1 attenuated AIA. Therefore, the sFasL-DR5 interaction promotes inflammation and is a potential therapeutic target., Competing Interests: DJ, HK, HK, MK, HJ, YO, DK, JK, SC, YJ, EL, SL, ES, HK, EY, DC No competing interests declared, (© 2021, Jeong et al.)

Asthma is a common pulmonary disease with several different forms. The most studied form of asthma is the allergic form, which is mainly related to the function of Th2 cells and their production of cytokines (IL-4, IL-5, and IL-13) in association with allergen sensitization and adaptive immunity. Recently, there have been many advances in understanding non-allergic asthma, which seems to be related to environmental factors such as air pollution, infection, or even obesity. Cells of the innate immune system, including macrophages, neutrophils, and natural killer T cells as well as the newly described innate lymphoid cells, are effective producers of a variety of cytokines and seem to play important roles in the development of non-allergic asthma. In this review, we focus on recent findings regarding innate lymphoid cells and their roles in asthma.