STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells

Kahlfuß, Sascha; Kaufmann, Ulrike; Concepcion, Axel R.; Noyer, Lucile; Raphael, Dimitrius; Vaeth, Martin; Yang, Jun J.; Pancholi, Priya; Maus, Máté; Muller, James; Kozhaya, Lina; Khodadadi‐Jamayran, Alireza; Sun, Zhengxi; Shaw, Patrick J.; Unutmaz, Derya; Stathopulos, Peter B.; Feist, Cori; Cameron, Scott; Turvey, Stuart E.; Feske, Stefan

doi:10.15252/emmm.201911592

Cited by 30 publications

(30 citation statements)

References 89 publications

(149 reference statements)

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“…Importantly, preventing calcium influx through genetic deletion of components of the calcium release-activated calcium channel (CRAC) pathway impairs CD8 + CTL effector function and antitumor immunity in mouse models for melanoma and colon carcinoma (132). In addition to calcium also sodium was shown to regulate T cell function, more precisely, the effector function of Th17 cells (133)(134)(135)(136). However, the role of sodium on effector T cell function within the TME is elusive.…”

Section: The Tumor Microenvironment (Tme)mentioning

confidence: 99%

Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

et al. 2021

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The function of T cells is critically dependent on their ability to generate metabolic building blocks to fulfil energy demands for proliferation and consecutive differentiation into various T helper (Th) cells. Th cells then have to adapt their metabolism to specific microenvironments within different organs during physiological and pathological immune responses. In this context, Th2 cells mediate immunity to parasites and are involved in the pathogenesis of allergic diseases including asthma, while CD8+ T cells and Th1 cells mediate immunity to viruses and tumors. Importantly, recent studies have investigated the metabolism of Th2 cells in more detail, while others have studied the influence of Th2 cell-mediated type 2 immunity on the tumor microenvironment (TME) and on tumor progression. We here review recent findings on the metabolism of Th2 cells and discuss how Th2 cells contribute to antitumor immunity. Combining the evidence from both types of studies, we provide here for the first time a perspective on how the energy metabolism of Th2 cells and the TME interact. Finally, we elaborate how a more detailed understanding of the unique metabolic interdependency between Th2 cells and the TME could reveal novel avenues for the development of immunotherapies in treating cancer.

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Section: The Tumor Microenvironment (Tme)mentioning

confidence: 99%

Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

et al. 2021

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“…Pathogenic T helper (Th)17 cells are involved in several autoimmune diseases, including MS and Crohn's disease [31], while physiological Th17 cell immune responses mediate immunity to fungi such as Candida albicans [32] and extracellular bacteria [33]. Pathogenic Th17 cells were shown to be dependent on the ABC transporters ABCB1 (also known as multidrug resistance protein 1, MDR1) and the multidrug-resistance-associatedprotein-4 (MRP4) [34] (Figure 3).…”

Section: Abc Transporters In Cd4 + T Helper Cell Populationsmentioning

confidence: 99%

ABC Transporters in T Cell-Mediated Physiological and Pathological Immune Responses

Thurm

Schraven

Kahlfuß

2021

IJMS

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ATP-binding cassette (ABC) transporters represent a heterogeneous group of ATP-dependent transport proteins, which facilitate the import and/or export of various substrates, including lipids, sugars, amino acids and peptides, ions, and drugs. ABC transporters are involved in a variety of physiological processes in different human tissues. More recent studies have demonstrated that ABC transporters also regulate the development and function of different T cell populations, such as thymocytes, Natural Killer T cells, CD8+ T cells, and CD4+ T helper cells, including regulatory T cells. Here, we review the current knowledge on ABC transporters in these T cell populations by summarizing how ABC transporters regulate the function of the individual cell types and how this affects the immunity to viruses and tumors, and the course of autoimmune diseases. Furthermore, we provide a perspective on how a better understanding of the function of ABC transporters in T cells might provide promising novel avenues for the therapy of autoimmunity and to improve immunity to infection and cancer.

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“…STIM1 deficiency manifests as recurrent bacterial infections, autoimmune hemolytic anemia, nephrotic syndrome, as well as dysmorphic features [ 37 ]. STIM1 is a calcium channel that was recently shown to influence Th17 cell metabolism, which is important for antifungal immunity [ 38 ]. Interestingly, similar to COPA, STIM1 deficiency resulted in increased type I IFN response, which was suggested to be due to loss of STIM1-mediated retention of STING in the ER [ 39 •• ].…”

Section: Monogenic Autoimmunity and Susceptibility To Infectionmentioning

confidence: 99%

Monogenic autoimmunity and infectious diseases: the double-edged sword of immune dysregulation

Bigley

Cooper

2021

Current Opinion in Immunology

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The study of monogenic autoimmune diseases has provided key insights into molecular mechanisms involved in development of autoimmunity and immune tolerance. It has also become clear that such inborn errors of immunity (IEIs) frequently present clinically not only with autoimmune diseases, but also frequently have increased susceptibility to infection. The genes associated with monogenic autoimmunity influence diverse functional pathways, and the resulting immune dysregulation also impacts the complex and coordinated immune response to pathogens, for example type I interferon and cytokine signaling, the complement pathway and proper differentiation of the immune response. The SARS-CoV-2 pandemic has highlighted how monogenic autoimmunity can increase risk for serious infection with the discovery of severe disease in patients with pre-existing antibodies to Type I IFNs. This review discusses recent insight into the relationship between monogenic autoimmunity and infectious diseases.

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STIM1‐mediated calcium influx controls antifungal immunity and the metabolic function of non‐pathogenic Th17 cells

Cited by 30 publications

References 89 publications

Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

Metabolic Interdependency of Th2 Cell-Mediated Type 2 Immunity and the Tumor Microenvironment

ABC Transporters in T Cell-Mediated Physiological and Pathological Immune Responses

Monogenic autoimmunity and infectious diseases: the double-edged sword of immune dysregulation

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