The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity

Chan, Pamela; Silva, Eugenio Antonio Carrera; Kouchkovsky, Dimitri de; Joannas, Leonel; Hao, Liming; Hu, Donglei; Huntsman, Scott; Eng, Celeste; Licona-Limón, Paula; Weinstein, Jason S.; Herbert, De’Broski R.; Craft, Joseph; Flavell, Richard A.; Repetto, Silvia; Correale, Jorge; Burchard, Esteban G.; Torgerson, Dara G.; Ghosh, Sourav; Rothlin, Carla V.

doi:10.1126/science.aaf1358

Cited by 72 publications

(70 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A negative feedback loop involving the receptor tyrosine kinase TYRO3 in cDCs and its agonist PROS1 in T cells provides one such example (Fig 2). 11 Notably, the localization of an asthma-associated single nucleotide polymorphism within putative transcription factor binding sites of TYRO3 led to this discovery. Transcriptomic and proteomic analysis of human DCs treated with a cocktail of T H 2-licensing mediators revealed overexpression of multiple genes/proteins beyond those known to be T H 2 linked (eg, OX40 ligand [OX40L] and GATA3 ).…”

Section: Th2 Differentiation and T-cell Trafficking In Asthmatic Patimentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Asthma encompasses a variety of clinical phenotypes that involve distinct T cell–driven inflammatory processes. Improved understanding of human T-cell biology and the influence of innate cytokines on T-cell responses at the epithelial barrier has led to new asthma paradigms. This review captures recent knowledge on pathogenic CD4+ T cells in asthmatic patients by drawing on observations in mouse models and human disease. In patients with allergic asthma, TH2 cells promote IgE-mediated sensitization, airway hyperreactivity, and eosinophilia. Here we discuss recent discoveries in the myriad molecular pathways that govern the induction of TH2 differentiation and the critical role of GATA-3 in this process. We elaborate on how cross-talk between epithelial cells, dendritic cells, and innate lymphoid cells translates to T-cell outcomes, with an emphasis on the actions of thymic stromal lymphopoietin, IL-25, and IL-33 at the epithelial barrier. New concepts on how T-cell skewing and epitope specificity are shaped by multiple environmental cues integrated by dendritic cell “hubs” are discussed. We also describe advances in understanding the origins of atypical TH2 cells in asthmatic patients, the role of TH1 cells and other non-TH2 types in asthmatic patients, and the features of T-cell pathogenicity at the single-cell level. Progress in technologies that enable highly multiplexed profiling of markers within a single cell promise to overcome barriers to T-cell discovery in human asthmatic patients that could transform our understanding of disease. These developments, along with novel T cell–based therapies, position us to expand the assortment of molecular targets that could facilitate personalized treatments.

show abstract

Section: Th2 Differentiation and T-cell Trafficking In Asthmatic Patimentioning

confidence: 99%

Pathogenic CD4 + T cells in patients with asthma

Muehling

Lawrence

Woodfolk

2017

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

show abstract

“…Neutralization of Mer receptors in human dendritic cells results in enhanced T cell proliferative cytokine responses, showing that TAM signaling can directly inhibit T cell activation [75]. Recently, a central role for Tyro3 receptors in limiting type 2 immunity against helminthes and allergens has been revealed, both for humans and for mice [76]. Interestingly, Tyro3 is only involved in lymphocyte T helper 2 (Th2) responses, without affecting the Th1 counterparts [76].…”

Section: Tam-mediated Regulation Of Immunitymentioning

confidence: 99%

“…Recently, a central role for Tyro3 receptors in limiting type 2 immunity against helminthes and allergens has been revealed, both for humans and for mice [76]. Interestingly, Tyro3 is only involved in lymphocyte T helper 2 (Th2) responses, without affecting the Th1 counterparts [76]. This specificity is assured by the fact that IL-4, the master cytokine in Th2 commitment, maintains the expression of the Tyro3 and Pros1, the major TAM signaling components involved in TAM-dependent Th2 regulation [73,76].…”

Section: Tam-mediated Regulation Of Immunitymentioning

confidence: 99%

“…Interestingly, Tyro3 is only involved in lymphocyte T helper 2 (Th2) responses, without affecting the Th1 counterparts [76]. This specificity is assured by the fact that IL-4, the master cytokine in Th2 commitment, maintains the expression of the Tyro3 and Pros1, the major TAM signaling components involved in TAM-dependent Th2 regulation [73,76]. Thus, TAM signaling functions as a bi-directional integrator of the innate and adaptive immune systems, capable of adapting the magnitude and specificity of immune responses.…”

Section: Tam-mediated Regulation Of Immunitymentioning

confidence: 99%

See 1 more Smart Citation

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

Paolino

Penninger

2016

Cancers

View full text Add to dashboard Cite

The TAM receptor protein tyrosine kinases—Tyro3, Axl, and Mer—are essential regulators of immune homeostasis. Guided by their cognate ligands Growth arrest-specific gene 6 (Gas6) and Protein S (Pros1), these receptors ensure the resolution of inflammation by dampening the activation of innate cells as well as by restoring tissue function through promotion of tissue repair and clearance of apoptotic cells. Their central role as negative immune regulators is highlighted by the fact that deregulation of TAM signaling has been linked to the pathogenesis of autoimmune, inflammatory, and infectious diseases. Importantly, TAM receptors have also been associated with cancer development and progression. In a cancer setting, TAM receptors have a dual regulatory role, controlling the initiation and progression of tumor development and, at the same time, the associated anti-tumor responses of diverse immune cells. Thus, modulation of TAM receptors has emerged as a potential novel strategy for cancer treatment. In this review, we discuss our current understanding of how TAM receptors control immunity, with a particular focus on the regulation of anti-tumor responses and its implications for cancer immunotherapy.

show abstract

“…A gátlás az I. típusú IFN receptor (IFNAR) aktiválásával, SOCS1 és SOCS3 (Suppressor of cytokine signaling-1, -3) molekulákon keresztül valósul meg [29,30]. A TYRO3 gyulladás gátló hatása allergiás reakciókban és a paraziták elleni 2-es típusú immunválaszban is igazolt [31]. …”

Section: A Veleszületett Immunválasz Szabályozásaunclassified

A gyulladásos bélbetegségek patogenezisében szerepet játszó gének és mikroRNS-ek azonosítása módosított mintagyűjtéssel

Boros

View full text Add to dashboard Cite

The TAM family receptor tyrosine kinase TYRO3 is a negative regulator of type 2 immunity

Cited by 72 publications

References 41 publications

Pathogenic CD4 + T cells in patients with asthma

Pathogenic CD4 + T cells in patients with asthma

The Role of TAM Family Receptors in Immune Cell Function: Implications for Cancer Therapy

A gyulladásos bélbetegségek patogenezisében szerepet játszó gének és mikroRNS-ek azonosítása módosított mintagyűjtéssel

Contact Info

Product

Resources

About