Preprint / Version 1

Regulators, processes, and intricacies of the Innate Immune System

##article.authors##

  • Arjun Yedavalli University of Texas at Dallas

DOI:

https://doi.org/10.58445/rars.1092

Keywords:

immune, immune system, biotechnology, innate immune system, luciferase

Abstract

Insight into immune system regulation is critical to understanding the homeostasis of the immune system, diagnosis of various autoimmune diseases, and cancer prevention measures in the body. The immune system is incredibly complex, from the organ to tissue to cell to molecular level. The innate immune system is contained within each somatic cell, capable of reacting to pathogen and damage-associated molecular patterns via pattern recognition receptors. These receptors initiate innate immune pathways that lead to inflammation. Understanding the mechanisms and regulators of the innate immune system and methods by which researchers map innate pathways provides a broader and more holistic context for the immune system's role in many diseases and disorders. To that end, this paper aims to record and analyze multiple proteins and mechanisms of the innate immune system, structural/functional elements of proteins that contribute to immune regulation of the NEMO (IKK-γ) complex with a focus on leucine-rich repeat regions, standard methodologies for testing signal pathways, and limitations/possible new methods for immune testing.

References

Bella, J., Hindle, K. L., McEwan, P. A., & Lovell, S. C. (2008). The leucine-rich repeat structure. Cellular and Molecular Life Sciences: CMLS, 65(15), 2307–2333. https://doi.org/10.1007/s00018-008-8019-0

Cabello-Verrugio, C., Santander, C., Cofré, C., Acuña, M. J., Melo, F., & Brandan, E. (2012). The Internal Region Leucine-rich Repeat 6 of Decorin Interacts with Low Density Lipoprotein Receptor-related Protein-1, Modulates Transforming Growth Factor (TGF)-β-dependent Signaling, and Inhibits TGF-β-dependent Fibrotic Response in Skeletal Muscles. Journal of Biological Chemistry, 287(9), 6773–6787. https://doi.org/10.1074/jbc.m111.312488

Carter, M., Essner, R., Goldstein, N., & Iyer, M. (2022, January 1). Chapter 14 - Intracellular Signaling and Biochemical Assays (M. Carter, R. Essner, N. Goldstein, & M. Iyer, Eds.). ScienceDirect; Academic Press. https://www.sciencedirect.com/science/article/pii/B9780128186466000014

Chiu, H.-W., Wu, C.-H., Lin, W.-Y., Wong, W.-T., Tsai, W.-C., Hsu, H.-T., Ho, C.-L., Cheng, S.-M., Cheng, C.-C., Yang, S.-P., Li, L.-H., & Hua, K.-F. (2024). The Angiotensin II Receptor Neprilysin Inhibitor LCZ696 Inhibits the NLRP3 Inflammasome By Reducing Mitochondrial Dysfunction in Macrophages and Alleviates Dextran Sulfate Sodium-induced Colitis in a Mouse Model. Inflammation. https://doi.org/10.1007/s10753-023-01939-7

Cui, J., Chen, Y., Wang, H. Y., & Wang, R.-F. (2014). Mechanisms and pathways of innate immune activation and regulation in health and cancer. Human Vaccines & Immunotherapeutics, 10(11), 3270–3285. https://doi.org/10.4161/21645515.2014.979640

Cui, J., Zhu, L., Xia, X., Wang, H. Y., Legras, X., Hong, J., Ji, J., Shen, P., Zheng, S., Chen, Z. J., & Wang, R.-F. (2010). NLRC5 Negatively Regulates the NF-κB and Type I Interferon Signaling Pathways. Cell, 141(3), 483–496. https://doi.org/10.1016/j.cell.2010.03.040

Ibeagha-Awemu, E. M., Peters, S. O., Akwanji, K. A., Imumorin, I. G., & Zhao, X. (2016). High density genome wide genotyping-by-sequencing and association identifies common and low frequency SNPs, and novel candidate genes influencing cow milk traits. Scientific Reports, 6(1). https://doi.org/10.1038/srep31109

Israel, A. (2009). The IKK Complex, a Central Regulator of NF- B Activation. Cold Spring Harbor Perspectives in Biology, 2(3), a000158–a000158. https://doi.org/10.1101/cshperspect.a000158

Kurien, B. T., & Scofield, R. H. (2015). Western Blotting: An Introduction. Methods in Molecular Biology, 1312, 17–30. https://doi.org/10.1007/978-1-4939-2694-7_5

Kwon, J. J., & Hahn, W. C. (2021). A Leucine-Rich Repeat Protein Provides a SHOC2 the RAS Circuit: a Structure-Function Perspective. Molecular and Cellular Biology, 41(4). https://doi.org/10.1128/mcb.00627-20

Liu, T., Tang, Q., Liu, K., Xie, W., Liu, X., Wang, H., Wang, R.-F., & Cui, J. (2016). TRIM11 Suppresses AIM2 Inflammasome by Degrading AIM2 via p62-Dependent Selective Autophagy. Cell Reports, 16(7), 1988–2002. https://doi.org/10.1016/j.celrep.2016.07.019

Lv, X., Li, S., Yu, Y., Jin, S., Zhang, X., & Li, F. (2023). LvCD14L Acts as a Novel Pattern Recognition Receptor and a Regulator of the Toll Signaling Pathway in Shrimp. International Journal of Molecular Sciences, 24(9), 7770. https://doi.org/10.3390/ijms24097770

Matsushima, N., Takatsuka, S., Miyashita, H., & Kretsinger, R. H. (2019). Leucine Rich Repeat Proteins: Sequences, Mutations, Structures and Diseases. Protein & Peptide Letters, 26(2), 108–131. https://doi.org/10.2174/0929866526666181208170027

Meng, Q., Cai, C., Sun, T., Wang, Q., Xie, W., Wang, R., & Cui, J. (2015). Reversible ubiquitination shapes NLRC5 function and modulates NF-κB activation switch. Journal of Cell Biology, 211(5), 1025–1040. https://doi.org/10.1083/jcb.201505091

Neefjes, M., Housmans, B. a. C., van den Akker, G. G. H., van Rhijn, L. W., Welting, T. J. M., & van der Kraan, P. M. (2021). Reporter gene comparison demonstrates interference of complex body fluids with secreted luciferase activity. Scientific Reports, 11(1), 1359. https://doi.org/10.1038/s41598-020-80451-6

Oeckinghaus, A., & Ghosh, S. (2009). The NF- B Family of Transcription Factors and Its Regulation. Cold Spring Harbor Perspectives in Biology, 1(4), a000034–a000034. https://doi.org/10.1101/cshperspect.a000034

Paysan-Lafosse, T., Blum, M., Chuguransky, S., Grego, T., Pinto, B. L., Salazar, G., Bileschi, M., Bork, P., Bridge, A., Colwell, L., Gough, J., Haft, D., Letunić, I., Marchler-Bauer, A., Mi, H., Natale, D., Orengo, C., Pandurangan, A., Rivoire, C., & Sigrist, C. J. A. (2022). InterPro in 2022. Nucleic Acids Research, 51(D1). https://doi.org/10.1093/nar/gkac993

Seok, J. K., Kang, H. C., Cho, Y.-Y., Lee, H. S., & Lee, J. Y. (2021). Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases. Archives of Pharmacal Research, 44(1), 16–35. https://doi.org/10.1007/s12272-021-01307-9

Wu, C., Su, Z., Lin, M., Ou, J., Zhao, W., Cui, J., & Rong Fu Wang. (2017). NLRP11 attenuates Toll-like receptor signalling by targeting TRAF6 for degradation via the ubiquitin ligase RNF19A. Nature Communications, 8(1). https://doi.org/10.1038/s41467-017-02073-3

Wu, C., Yang, Y., Ou, J., Zhu, L., Zhao, W., & Cui, J. (2016). LRRC14 attenuates Toll-like receptor-mediated NF-κB signaling through disruption of IKK complex. Experimental Cell Research, 347(1), 65–73. https://doi.org/10.1016/j.yexcr.2016.07.011

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2024-04-13

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