Published March 13, 2023 | Version v1
Publication Open

Regulation of the immune system by the insulin receptor in health and disease

Creators

  • 1. University of Toronto
  • 2. Buck Institute for Research on Aging
  • 3. University of Alberta
  • 4. University Health Network
  • 5. Toronto General Hospital
  • 6. Austral University
  • 7. Consejo Nacional de Investigaciones Científicas y Técnicas
  • 8. Stanford University
  • 9. University of Southern California

Description

The signaling pathways downstream of the insulin receptor (InsR) are some of the most evolutionarily conserved pathways that regulate organism longevity and metabolism. InsR signaling is well characterized in metabolic tissues, such as liver, muscle, and fat, actively orchestrating cellular processes, including growth, survival, and nutrient metabolism. However, cells of the immune system also express the InsR and downstream signaling machinery, and there is increasing appreciation for the involvement of InsR signaling in shaping the immune response. Here, we summarize current understanding of InsR signaling pathways in different immune cell subsets and their impact on cellular metabolism, differentiation, and effector versus regulatory function. We also discuss mechanistic links between altered InsR signaling and immune dysfunction in various disease settings and conditions, with a focus on age related conditions, such as type 2 diabetes, cancer and infection vulnerability.

⚠️ This is an automatic machine translation with an accuracy of 90-95%

Translated Description (Arabic)

مسارات الإشارات أسفل مجرى مستقبلات الأنسولين (InsR) هي بعض من أكثر المسارات المحفوظة تطوريًا والتي تنظم طول عمر الكائن الحي والتمثيل الغذائي. تتميز إشارات InsR بشكل جيد في الأنسجة الأيضية، مثل الكبد والعضلات والدهون، وتنسق بنشاط العمليات الخلوية، بما في ذلك النمو والبقاء والتمثيل الغذائي للمغذيات. ومع ذلك، فإن خلايا الجهاز المناعي تعبر أيضًا عن InsR وآلية الإشارات النهائية، وهناك تقدير متزايد لمشاركة إشارات InsR في تشكيل الاستجابة المناعية. هنا، نلخص الفهم الحالي لمسارات إشارات InsR في مجموعات فرعية مختلفة من الخلايا المناعية وتأثيرها على التمثيل الغذائي الخلوي والتمايز والوظيفة المستجيبة مقابل الوظيفة التنظيمية. كما نناقش الروابط الميكانيكية بين إشارات InsR المتغيرة والخلل الوظيفي المناعي في مختلف بيئات وظروف المرض، مع التركيز على الحالات المرتبطة بالعمر، مثل مرض السكري من النوع 2 والسرطان والضعف تجاه العدوى.

Translated Description (French)

Les voies de signalisation en aval du récepteur de l'insuline (InsR) sont parmi les voies les plus conservées de l'évolution qui régulent la longévité et le métabolisme de l'organisme. La signalisation InsR est bien caractérisée dans les tissus métaboliques, tels que le foie, les muscles et la graisse, orchestrant activement les processus cellulaires, y compris la croissance, la survie et le métabolisme des nutriments. Cependant, les cellules du système immunitaire expriment également l'InsR et les mécanismes de signalisation en aval, et l'implication de la signalisation InsR dans la mise en forme de la réponse immunitaire est de plus en plus appréciée. Ici, nous résumons la compréhension actuelle des voies de signalisation InsR dans différents sous-ensembles de cellules immunitaires et leur impact sur le métabolisme cellulaire, la différenciation et la fonction effectrice par rapport à la fonction régulatrice. Nous discutons également des liens mécanistes entre la signalisation InsR altérée et le dysfonctionnement immunitaire dans divers contextes et conditions pathologiques, en mettant l'accent sur les conditions liées à l'âge, telles que le diabète de type 2, le cancer et la vulnérabilité aux infections.

Translated Description (Spanish)

Las vías de señalización aguas abajo del receptor de insulina (InsR) son algunas de las vías más conservadas evolutivamente que regulan la longevidad y el metabolismo del organismo. La señalización de InsR está bien caracterizada en los tejidos metabólicos, como el hígado, el músculo y la grasa, orquestando activamente los procesos celulares, incluido el crecimiento, la supervivencia y el metabolismo de nutrientes. Sin embargo, las células del sistema inmunitario también expresan la maquinaria de señalización de InsR y aguas abajo, y hay una apreciación creciente por la participación de la señalización de InsR en la configuración de la respuesta inmunitaria. Aquí, resumimos la comprensión actual de las vías de señalización de InsR en diferentes subconjuntos de células inmunitarias y su impacto en el metabolismo celular, la diferenciación y la función efectora frente a la reguladora. También discutimos los vínculos mecanicistas entre la señalización InsR alterada y la disfunción inmune en diversos entornos y afecciones de enfermedades, con un enfoque en las afecciones relacionadas con la edad, como la diabetes tipo 2, el cáncer y la vulnerabilidad a las infecciones.

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Additional details

Additional titles

Translated title (Arabic)
تنظيم الجهاز المناعي من قبل مستقبلات الأنسولين في الصحة والمرض
Translated title (French)
Régulation du système immunitaire par le récepteur de l'insuline dans la santé et la maladie
Translated title (Spanish)
Regulación del sistema inmunitario por el receptor de insulina en la salud y la enfermedad

Identifiers

Other
https://openalex.org/W4324088613
DOI
10.3389/fendo.2023.1128622

Is supplement to
https://openalex.org/W4389947743 (Other)
https://openalex.org/W4387949432 (Other)
https://openalex.org/W4298235256 (Other)
https://openalex.org/W4232068572 (Other)
https://openalex.org/W2899214804 (Other)
https://openalex.org/W2344451212 (Other)
https://openalex.org/W2283191725 (Other)
https://openalex.org/W2139329774 (Other)
https://openalex.org/W2083552703 (Other)
https://openalex.org/W2018711046 (Other)

GreSIS Basics Section

Is Global South Knowledge
Yes
Country
Argentina

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