IL-12p40 Monomer: A Potential Player in Macrophage Regulation

Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-function...

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Main Authors: Brian Jeong, Kalipada Pahan
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Immuno
Subjects:
Online Access:https://www.mdpi.com/2673-5601/4/1/5
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author Brian Jeong
Kalipada Pahan
author_facet Brian Jeong
Kalipada Pahan
author_sort Brian Jeong
collection DOAJ
description Macrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine of the IL-12 family. However, new research has emerged that demonstrates that this p40 monomer may play a bigger role in shaping immune environments. To shed light on the specific effects of p40 monomer on macrophages and their surrounding environment, we showed, through cell culture studies, qPCR, ELISA, and immunofluorescence analyses, that the direct administration of recombinant p40 monomer to RAW 264.7 cells and primary lung macrophages stimulated the production of both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals. Accordingly, p40 monomer prevented the full pro-inflammatory effects of LPS, and the neutralization of p40 monomer by mAb a3-3a stimulated the pro-inflammatory effects of LPS. Furthermore, we demonstrated that the intranasal administration of p40 monomer upregulated TNFα<sup>+</sup>IL-10<sup>+</sup> macrophages in vivo in the lungs of mice. Collectively, these results indicate an important immunoregulatory function of p40 monomer in the upregulation of both pro- and anti-inflammatory molecules in macrophages.
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spelling doaj.art-0cfb7f8fffa74789a46ef86e75d2af8a2024-03-27T13:46:47ZengMDPI AGImmuno2673-56012024-02-0141779010.3390/immuno4010005IL-12p40 Monomer: A Potential Player in Macrophage RegulationBrian Jeong0Kalipada Pahan1Department of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USADepartment of Neurological Sciences, Rush University Medical Center, Chicago, IL 60612, USAMacrophages are myeloid phagocytic leukocytes whose functions are to protect against infections, mediate T-cell responses, and maintain tissue homeostasis. IL-12p40 monomer is a cytokine that is largely produced by macrophages, and it has, for the longest time, been considered a largely non-functional cytokine of the IL-12 family. However, new research has emerged that demonstrates that this p40 monomer may play a bigger role in shaping immune environments. To shed light on the specific effects of p40 monomer on macrophages and their surrounding environment, we showed, through cell culture studies, qPCR, ELISA, and immunofluorescence analyses, that the direct administration of recombinant p40 monomer to RAW 264.7 cells and primary lung macrophages stimulated the production of both pro-inflammatory (TNFα) and anti-inflammatory (IL-10) signals. Accordingly, p40 monomer prevented the full pro-inflammatory effects of LPS, and the neutralization of p40 monomer by mAb a3-3a stimulated the pro-inflammatory effects of LPS. Furthermore, we demonstrated that the intranasal administration of p40 monomer upregulated TNFα<sup>+</sup>IL-10<sup>+</sup> macrophages in vivo in the lungs of mice. Collectively, these results indicate an important immunoregulatory function of p40 monomer in the upregulation of both pro- and anti-inflammatory molecules in macrophages.https://www.mdpi.com/2673-5601/4/1/5macrophageIL-12p40 monomerIL-10TNFαimmunomodulation
spellingShingle Brian Jeong
Kalipada Pahan
IL-12p40 Monomer: A Potential Player in Macrophage Regulation
Immuno
macrophage
IL-12p40 monomer
IL-10
TNFα
immunomodulation
title IL-12p40 Monomer: A Potential Player in Macrophage Regulation
title_full IL-12p40 Monomer: A Potential Player in Macrophage Regulation
title_fullStr IL-12p40 Monomer: A Potential Player in Macrophage Regulation
title_full_unstemmed IL-12p40 Monomer: A Potential Player in Macrophage Regulation
title_short IL-12p40 Monomer: A Potential Player in Macrophage Regulation
title_sort il 12p40 monomer a potential player in macrophage regulation
topic macrophage
IL-12p40 monomer
IL-10
TNFα
immunomodulation
url https://www.mdpi.com/2673-5601/4/1/5
work_keys_str_mv AT brianjeong il12p40monomerapotentialplayerinmacrophageregulation
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