Effects of the storage conditions on the stability of natural and synthetic cannabis in biological matrices for forensic toxicology analysis: An update from the literature
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PRDM1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
Aliases | PRDM1, BLIMP1, PRDI-BF1, PR domain 1, PR/SET domain 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 603423; MGI: 99655; HomoloGene: 925; GeneCards: PRDM1; OMA:PRDM1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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PR domain zinc finger protein 1, or B lymphocyte-induced maturation protein-1 (BLIMP-1), is a protein in humans encoded by the gene PRDM1 located on chromosome 6q21.[5] BLIMP-1 is considered a 'master regulator' of hematopoietic stem cells, and plays a critical role in the development of plasma B cells, T cells, dendritic cells (DCs), macrophages, and osteoclasts. Pattern Recognition Receptors (PRRs) can activate BLIMP-1, both as a direct target and through downstream activation.[6][7][8] BLIMP-1 is a transcription factor that triggers expression of many downstream signaling cascades.[6][9][10][11] As a fine-tuned and contextual rheostat of the immune system, BLIMP-1 up- or down-regulates immune responses depending on the precise scenarios.[6][10][12] BLIMP-1 is highly expressed in exhausted T-cells – clones of dysfunctional T-cells with diminished functions due to chronic immune response against cancer, viral infections, or organ transplant.[7][8][13][14]
Function
![The regulatory role of BLIMP-1/PRDM1 on immunocytokines and hematopoietic cells.](https://upload.wikimedia.org/wikipedia/commons/thumb/d/da/The_regulatory_role_of_BLIMP-1_on_immunocytokines_and_hematopoietic_cells.png/220px-The_regulatory_role_of_BLIMP-1_on_immunocytokines_and_hematopoietic_cells.png)
As a potent repressor of beta-interferon (IFN-β), BLIMP-1 competes for interferon regulatory factors (IRF) binding sites in the IFN-β promoter due to its sequence similarity with IRF1 and IRF2.[6][9] However, BLIMP-1 cools down and activates immune responses in a highly contextual manner. BLIMP-1 represses NFκB/TNF-R pathway repressor NLRP12, thus indirectly activating the immune response.[6] BLIMP-1 expression is also upregulated by danger signals from double-stranded RNA (specific to virus), lipopolysaccharides (specific to gram-negative bacteria), unmethylated CpG DNA (abundant in bacterial genomes), and cancer inflammation via Toll-like receptor (TLR) 3, TLR-4, TLR-9, and STAT signaling, respectively.[6][9]
The increased expression of the BLIMP-1 protein in B lymphocytes, T lymphocytes, NK cells and other immune system cells leads to an immune response through proliferation and differentiation of antibody secreting plasma cells. In a monocytic cell line, over-expression of BLIMP-1 can lead to differentiation into mature macrophages. BLIMP-1 also plays a role in osteoclastogenesis as well as in the modulation of dendritic cells. Other cells of the immune system such as human peripheral blood monocytes and granulocytes also express BLIMP-1.[6][10][11]
As a transcriptional repressor, BLIMP-1 has a critical role in the foundation of the mouse germ cell lineage, as its disruption causes a block early in the process of primordial germ cell formation. BLIMP-1-deficient mutant embryos form a tight cluster of about 20 primordial germ cell-like cells, which fail to show the characteristic migration, proliferation and consistent repression of homeobox genes that normally accompany specification of primordial germ cells. BLIMP-1 is widely expressed in stem cells of developing embryos.[6] The genetic lineage-tracing experiments indicate that the BLIMP-1-positive cells originating from the proximal posterior epiblast cells are indeed the lineage-restricted primordial germ cell precursors.[15]
B cell development
BLIMP-1 is an important regulator of plasma cell differentiation. During B cell development, a B cell can either differentiate into a short-lived plasma cell or into a germinal center B cell after receiving proper activation and co-stimulation.[6][10] BLIMP-1 acts as a master gene regulating the transcriptional network that regulates B cell terminal differentiation. Except for naïve and memory B cells, all antibody secreting cells express BLIMP-1 regardless of their location and differentiation history.[5] BLIMP-1 directly initiates unfolded protein response (UPR) by activating Ire1, Xbp1, and Arf6, allowing the plasma B cells to produce vast amounts of antibody.[6][12] BLIMP-1 expression is carefully controlled: the expression of BLIMP-1 is low or undetectable in primary B cells, and only upregulated in plasmablasts and plasma cells.[16] BLIMP-1 is a direct transcriptional target of IRF-4, which is also necessary for B-cell differentiation.[6] The premature expression of BLIMP-1 in primary B cells results in cell death, so only cells that are ready to initiate transcription driven by BLIMP-1 are able to survive and differentiate.[5][13] However, without BLIMP-1, proliferating B cells are unable to differentiate to plasma cells, resulting in severe reduction in production of all isotypes of immunoglobulin.[5]
T cell development
BLIMP-1 promotes naive T-cells to differentiate into T-helper (Th) 2 lineage, while repressing the differentiation into Th1, Th17, and follicular Th.[9] BLIMP-1 is also required for differentiation of cytotoxic T-cell.[13] Specifically, the expression of granzyme B (a source of cytotoxicity) in Tc depends on the presence of BLIMP-1 and interleukin-2 (IL-2) cytokine.[6][9]
BLIMP-1 is a gatekeeper of T-cell activation and plays a key role in maintaining normal T cell homeostasis. BLIMP-1 deficiency leads to high numbers of activated T helper cells and severe autoimmune diseases in laboratory mice.[13] BLIMP-1 is important in dampening autoimmunity, as well as antiviral and antitumor responses.[13] BLIMP-1 regulates T cell activation through a negative feedback loop: T cell activation leads to IL-2 production, IL-2 leads to PRDM1 transcription, and BLIMP-1 feeds back to repress IL-2 gene transcription.[5]
T cell exhaustion
Multiple studies have reported high expression of BLIMP-1 in exhausted T cells.[13][14] T cell exhaustion is usually a result of chronic immune activations, commonly caused by viral infection (e.g. HIV), cancer, or organ transplant.[7][13][14] High expression of BLIMP-1 in Tc and Th cells is associated with the transcription of receptors inhibiting immune responses, though it is unclear whether the relation between BLIMP-1 expression and T-cell exhaustion is causal or just associative.[8]
BLIMP-1 helps the production of short-lived effector T cells and clonally exhausted T cells. It also helps with the migration of T cells out of the spleen and lymph nodes into peripheral tissues. However, BLIMP-1 does not promote the production of long-lived effector memory cells. BLIMP-1 allows the production of some longer lived effector memory cells but its absence allows for the generation of long term central memory cells, which are thought to have a higher potential of proliferation on secondary challenge.[17]
DCs and macrophages development
BLIMP-1 has been shown in vitro as a cell lineage determinant in monocytes, inducing their differentiation into DCs and macrophages. It is speculated to have the similar effects in vivo.[6][9] In addition, BLIMP-1 also suppressed myeloid cells from differentiating into granulocytes, which includes eosinophil, basophil, and neutrophils.[6][9] The role of BLIMP-1 in DCs and macrophages development is a matter of interest because analysis have suggested that DCs, rather than B-cells, is the way in which individual with single nucleotide polymorphisms (SNP) near BLIMP-1 (specifically, rs548234 in Han Chinese, and rs6568431 in European) are predisposed to Systemic Lupus Erythematosus (SLE).[6][9]
Osteoclast development
Osteoclasts are multinucleated cells that break down and resorb bone tissues.[6][18] Together with osteoblasts, which form new bones, osteoclast helps maintain and repair bone in vertebrates.[18] BLIMP-1 directly and indirectly represses anti-osteoclastogenesis genes such as Bcl6, IRF8, and MafB, helping monocytes differentiate into osteoclasts.[6] In mice, insufficient expression of BLIMP-1 in osteoclast progenitors would lead to abnormal development of the skeleton.[6]
Diseases related to BLIMP-1
SNPs near the PRDM1 gene have been identified in genome-wide association studies (GWAS) to be linked to lupus (SLE) and rheumatoid arthritis (RA).[9] BLIMP-1 represses the expression of the proinflammatory cytokine Interleukin-6 (IL-6), and cathepsin S (CTSS), which promotes antigen processing and presentation. BLIMP-1 deficiency and IL-6 overexpression were linked to inflammatory bowel disease (IBD) and SLE.[6]
Another GWAS has identified two genetic variations near the PRDM1 gene that predict an increased likelihood of developing a second cancer after radiation treatment for Hodgkin lymphoma.[19]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000057657 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000038151 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d e Boi M, Zucca E, Inghirami G, Bertoni F (May 2015). "PRDM1/BLIMP1: a tumor suppressor gene in B and T cell lymphomas". Leukemia & Lymphoma. 56 (5): 1223–1228. doi:10.3109/10428194.2014.953155. PMID 25115512. S2CID 7518347.
- ^ a b c d e f g h i j k l m n o p q r s Ulmert I, Henriques-Oliveira L, Pereira CF, Lahl K (December 2020). "Mononuclear phagocyte regulation by the transcription factor Blimp-1 in health and disease". Immunology. 161 (4): 303–313. doi:10.1111/imm.13249. PMC 7692253. PMID 32799350.
- ^ a b c Wells AD, Li XC, Strom TB, Turka LA (May 2001). "The role of peripheral T-cell deletion in transplantation tolerance". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 356 (1409): 617–623. doi:10.1098/rstb.2001.0845. PMC 1088449. PMID 11375065.
- ^ a b c Crawford A, Angelosanto JM, Kao C, Doering TA, Odorizzi PM, Barnett BE, Wherry EJ (February 2014). "Molecular and transcriptional basis of CD4⁺ T cell dysfunction during chronic infection". Immunity. 40 (2): 289–302. doi:10.1016/j.immuni.2014.01.005. PMC 3990591. PMID 24530057.
- ^ a b c d e f g h i Kim SJ (December 2015). "Immunological function of Blimp-1 in dendritic cells and relevance to autoimmune diseases". Immunologic Research. 63 (1–3): 113–120. doi:10.1007/s12026-015-8694-5. PMC 4651792. PMID 26376898.
- ^ a b c d Turner, C. Alexander; Mack, David H.; Davis, Mark M. (1994-04-22). "Blimp-1, a novel zinc finger-containing protein that can drive the maturation of B lymphocytes into immunoglobulin-secreting cells". Cell. 77 (2): 297–306. doi:10.1016/0092-8674(94)90321-2. ISSN 0092-8674. PMID 8168136. S2CID 46200658.
- ^ a b Sciammas R, Davis MM (May 2004). "Modular nature of Blimp-1 in the regulation of gene expression during B cell maturation". Journal of Immunology. 172 (9): 5427–5440. doi:10.4049/jimmunol.172.9.5427. PMID 15100284.
- ^ a b Tellier J, Nutt SL (January 2019). "Plasma cells: The programming of an antibody-secreting machine". European Journal of Immunology. 49 (1): 30–37. doi:10.1002/eji.201847517. hdl:11343/284565. PMID 30273443. S2CID 52901472.
- ^ a b c d e f g Fu SH, Yeh LT, Chu CC, Yen BL, Sytwu HK (July 2017). "New insights into Blimp-1 in T lymphocytes: a divergent regulator of cell destiny and effector function". Journal of Biomedical Science. 24 (1): 49. doi:10.1186/s12929-017-0354-8. PMC 5520377. PMID 28732506.
- ^ a b c Collier JL, Weiss SA, Pauken KE, Sen DR, Sharpe AH (July 2021). "Not-so-opposite ends of the spectrum: CD8+ T cell dysfunction across chronic infection, cancer and autoimmunity". Nature Immunology. 22 (7): 809–819. doi:10.1038/s41590-021-00949-7. PMC 9197228. PMID 34140679.
- ^ Ohinata Y, Payer B, O'Carroll D, Ancelin K, Ono Y, Sano M, et al. (July 2005). "Blimp1 is a critical determinant of the germ cell lineage in mice". Nature. 436 (7048): 207–213. Bibcode:2005Natur.436..207O. doi:10.1038/nature03813. PMID 15937476. S2CID 4399840.
- ^ Moroney JB, Chupp DP, Xu Z, Zan H, Casali P (December 2020). "Epigenetics of the antibody and autoantibody response". Current Opinion in Immunology. Autoimmunity. 67: 75–86. doi:10.1016/j.coi.2020.09.004. PMC 7744442. PMID 33176228.
- ^ Welsh RM (August 2009). "Blimp hovers over T cell immunity". Immunity. 31 (2): 178–180. doi:10.1016/j.immuni.2009.08.005. PMC 3220184. PMID 19699168.
- ^ a b Florencio-Silva R, Sasso GR, Sasso-Cerri E, Simões MJ, Cerri PS (2015-07-13). "Biology of Bone Tissue: Structure, Function, and Factors That Influence Bone Cells". BioMed Research International. 2015: 421746. doi:10.1155/2015/421746. PMC 4515490. PMID 26247020.
- ^ Best T, Li D, Skol AD, Kirchhoff T, Jackson SA, Yasui Y, et al. (July 2011). "Variants at 6q21 implicate PRDM1 in the etiology of therapy-induced second malignancies after Hodgkin's lymphoma". Nature Medicine. 17 (8): 941–943. doi:10.1038/nm.2407. PMC 3229923. PMID 21785431.
Further reading
- Huang S (July 1994). "Blimp-1 is the murine homolog of the human transcriptional repressor PRDI-BF1". Cell. 78 (1): 9. doi:10.1016/0092-8674(94)90565-7. PMID 8033216. S2CID 34007883.
- Mock BA, Liu L, LePaslier D, Huang S (October 1996). "The B-lymphocyte maturation promoting transcription factor BLIMP1/PRDI-BF1 maps to D6S447 on human chromosome 6q21-q22.1 and the syntenic region of mouse chromosome 10". Genomics. 37 (1): 24–28. doi:10.1006/geno.1996.0516. PMID 8921366.
- Ren B, Chee KJ, Kim TH, Maniatis T (January 1999). "PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins". Genes & Development. 13 (1): 125–137. doi:10.1101/gad.13.1.125. PMC 316372. PMID 9887105.
- Angelin-Duclos C, Cattoretti G, Lin KI, Calame K (November 2000). "Commitment of B lymphocytes to a plasma cell fate is associated with Blimp-1 expression in vivo". Journal of Immunology. 165 (10): 5462–5471. doi:10.4049/jimmunol.165.10.5462. PMID 11067898.
- Gupta S, Anthony A, Pernis AB (May 2001). "Stage-specific modulation of IFN-regulatory factor 4 function by Krüppel-type zinc finger proteins". Journal of Immunology. 166 (10): 6104–6111. doi:10.4049/jimmunol.166.10.6104. PMID 11342629.
- Medina F, Segundo C, Campos-Caro A, González-García I, Brieva JA (March 2002). "The heterogeneity shown by human plasma cells from tonsil, blood, and bone marrow reveals graded stages of increasing maturity, but local profiles of adhesion molecule expression". Blood. 99 (6): 2154–2161. doi:10.1182/blood.V99.6.2154. PMID 11877292. S2CID 135753.
- Shaffer AL, Lin KI, Kuo TC, Yu X, Hurt EM, Rosenwald A, et al. (July 2002). "Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program". Immunity. 17 (1): 51–62. doi:10.1016/S1074-7613(02)00335-7. PMID 12150891.
- Vasanwala FH, Kusam S, Toney LM, Dent AL (August 2002). "Repression of AP-1 function: a mechanism for the regulation of Blimp-1 expression and B lymphocyte differentiation by the B cell lymphoma-6 protooncogene". Journal of Immunology. 169 (4): 1922–1929. doi:10.4049/jimmunol.169.4.1922. PMID 12165517.
- Borson ND, Lacy MQ, Wettstein PJ (December 2002). "Altered mRNA expression of Pax5 and Blimp-1 in B cells in multiple myeloma". Blood. 100 (13): 4629–4639. doi:10.1182/blood.V100.13.4629. PMID 12453881.
- Györy I, Fejér G, Ghosh N, Seto E, Wright KL (March 2003). "Identification of a functionally impaired positive regulatory domain I binding factor 1 transcription repressor in myeloma cell lines". Journal of Immunology. 170 (6): 3125–3133. doi:10.4049/jimmunol.170.6.3125. PMID 12626569.
- Gyory I, Wu J, Fejér G, Seto E, Wright KL (March 2004). "PRDI-BF1 recruits the histone H3 methyltransferase G9a in transcriptional silencing". Nature Immunology. 5 (3): 299–308. doi:10.1038/ni1046. PMID 14985713. S2CID 33178299.
- Lotz C, Mutallib SA, Oehlrich N, Liewer U, Ferreira EA, Moos M, et al. (July 2005). "Targeting positive regulatory domain I-binding factor 1 and X box-binding protein 1 transcription factors by multiple myeloma-reactive CTL". Journal of Immunology. 175 (2): 1301–1309. doi:10.4049/jimmunol.175.2.1301. PMID 16002735.
- Tam W, Gomez M, Chadburn A, Lee JW, Chan WC, Knowles DM (May 2006). "Mutational analysis of PRDM1 indicates a tumor-suppressor role in diffuse large B-cell lymphomas". Blood. 107 (10): 4090–4100. doi:10.1182/blood-2005-09-3778. PMID 16424392.
- Pasqualucci L, Compagno M, Houldsworth J, Monti S, Grunn A, Nandula SV, et al. (February 2006). "Inactivation of the PRDM1/BLIMP1 gene in diffuse large B cell lymphoma". The Journal of Experimental Medicine. 203 (2): 311–317. doi:10.1084/jem.20052204. PMC 2118216. PMID 16492805.
- González-García I, Ocaña E, Jiménez-Gómez G, Campos-Caro A, Brieva JA (April 2006). "Immunization-induced perturbation of human blood plasma cell pool: progressive maturation, IL-6 responsiveness, and high PRDI-BF1/BLIMP1 expression are critical distinctions between antigen-specific and nonspecific plasma cells". Journal of Immunology. 176 (7): 4042–4050. doi:10.4049/jimmunol.176.7.4042. PMID 16547239.
- Garcia JF, Roncador G, García JF, Sánz AI, Maestre L, Lucas E, et al. (April 2006). "PRDM1/BLIMP-1 expression in multiple B and T-cell lymphoma". Haematologica. 91 (4): 467–474. PMID 16585013.
- Lim J, Hao T, Shaw C, Patel AJ, Szabó G, Rual JF, et al. (May 2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–814. doi:10.1016/j.cell.2006.03.032. PMID 16713569. S2CID 13709685.
External links
- PRDM1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- FactorBook PRDM1
This article incorporates text from the United States National Library of Medicine, which is in the public domain.