Abstract
Carassius auratus leukocyte immune-type receptors (CaLITRs) were recently discovered immunoregulatory receptors in goldfish that have diverse immunoglobulin-like (Ig-like) ectodomains and intracellular signaling motifs. Genomic analysis shows that CaLITR-types are also located as distinct gene clusters across multiple goldfish chromosomes. For example, CaLITR1 (unplaced) is a functionally ambiguous receptor having two Ig-like domains, a transmembrane domain (TM), and a short cytoplasmic tail (CYT) devoid of any recognizable signaling motifs. CaLITR2 (Chr47) is a putative inhibitory receptor containing four Ig-like domains, a TM, and a long CYT with an immunoreceptor tyrosine–based inhibition motif (ITIM) and immunoreceptor tyrosine–based switch motif (ITSM). A putative activating receptor-type, CaLITR3 (Chr3), has four Ig-like domains, a TM, and a short CYT containing a positively charged histidine residue and CaLITR4 (ChrLG28B) is a receptor with putative multifunctional signaling potential as well as five Ig-like domains, a TM, and a long tyrosine-motif containing CYT region. The variable genomic locations of the CaLITRs suggest that they are likely under the influence of different cis- and/or trans-regulatory elements. To better understand the transcriptional activities of select CaLITRs from variable genomic regions, we used an RT-qPCR–based approach to examine the expression of CaLITR1, CaLITR2, CaLITR3, and CaLITR4 during goldfish primary kidney macrophage (PKM) development and in mixed leukocyte reaction cultures (MLRs) of the goldfish. Our results showed that the select CaLITRs are differentially expressed during PKM development and in goldfish MLRs exposed to T-cell mitogens/immunosuppressive drugs, supporting that the transcription of these CaLITRs is likely regulated by distinct cis- and/or trans-regulatory elements.
Similar content being viewed by others
References
Ahn H, Kim J, Jeung EB, Lee GS (2014) Dimethyl sulfoxide inhibits NLRP3 inflammasome activation. Immunobiology 219(4):315–322
Barreda DR, Hanington PC, Stafford JL, Belosevic M (2005) A novel soluble form of the CSF-1 receptor inhibits proliferation of self-renewing macrophages of goldfish (Carassius auratus L.). Dev Comp Immunol 29(10):879–894
Barreda DR, Hanington PC, Walsh CK, Wong P, Belosevic M (2004) Differentially expressed genes that encode potential markers of goldfish macrophage development in vitro. Dev Comp Immunol 28(7–8):727–746
Barreda DR, Neumann NF, Belosevic M (2000) Flow cytometric analysis of PKH26-labeled goldfish kidney-derived macrophages. Dev Comp Immunol 24(4):395–406
Barrow AD, Martin CJ, Colonna M (2019) The natural cytotoxicity receptors in health and disease. Front Immunol 10:909
Barrow AD, Trowsdale J (2008) The extended human leukocyte receptor complex: diverse ways of modulating immune responses. Immunol Rev 224(1):98–123
Barrow AD, Trowsdale J (2006) You say ITAM and I say ITIM, let’s call the whole thing off: the ambiguity of immunoreceptor signalling. Eur J Immunol 36(7):1646–1653
Belosevic M, Hanington PC, Barreda DR (2006) Development of goldfish macrophages in vitro. Fish Shellfish Immunol 20(2):152–171
Bemer V, Truffa-Bachi P (1996) T cell activation by concanavalin A in the presence of cyclosporin A: immunosuppressor withdrawal induces NFATp translocation and interleukin-2 gene transcription. Eur J Immunol 26(7):1481–1488
Ben Mkaddem S, Benhamou M, Monteiro RC (2019) Understanding Fc receptor involvement in inflammatory diseases: from mechanisms to new therapeutic tools. Front Immunol 10:811
Brignall R, Cauchy P, Bevington SL, Gorman B, Pisco AO, Bagnall J, Paszek P (2017) Integration of kinase and calcium signaling at the level of chromatin underlies inducible gene activation in T cells. J Immunol 199(8):2652–2667
Canellada A, Ramirez BG, Minami T, Redondo JM, Cano E (2008) Calcium/calcineurin signaling in primary cortical astrocyte cultures: Rcan1-4 and cyclooxygenase-2 as NFAT target genes. Glia 56(7):709–722
Call ME, Wucherpfennig KW (2007) Common themes in the assembly and architecture of activating immune receptors. Nat Rev Immunol 7(11):841–850
Cantor H, Boyse EA (1975) Functional subclasses of T lymphocytes bearing different Ly antigens. II. Cooperation between subclasses of Ly+ cells in the generation of killer activity. Exp Med 141(6):1390–1399
Carreno BM, Collins M (2002) The B7 family of ligands and its receptors: new pathways of costimulation and inhibition of immune responses. Annu Rev Immunol 20:29
Caspi RR, Avtalion RR (1984) The mixed leukocyte reaction (MLR) in carp: bidirectional and unidirectional MLR responses. Dev Comp Immunol 8(3):631–637
Colombo D, Ammirati E (2011) Cyclosporine in transplantation-a history of converging timelines. J Biol Regul Homeost Agents 25(4):493–504
Cortes HD, Lillico DM, Zwozdesky MA, Pemberton JG, O’brien A, Montgomery BC, Stafford JL (2014) Induction of phagocytosis and intracellular signaling by an inhibitory channel catfish leukocyte immune-type receptor: evidence for immunoregulatory receptor functional plasticity in teleosts. J Innate Immun 6(4):435–455
Cichocki F, Hanson RJ, Lenvik T, Pitt M, McCullar V, Li H, Miller JS (2009) The transcription factor c-Myc enhances KIR gene transcription through direct binding to an upstream distal promoter element. Blood, Am J Hematol 113(14):3245–3253
de Abreu Costa L, Henrique Fernandes Ottoni M, Dos Santos MG, Meireles AB, de Gomes Almeida V, de Fátima Pereira W, Eustáquio Alvim Brito-Melo G (2017) Dimethyl sulfoxide (DMSO) decreases cell proliferation and TNF-α, IFN-γ, and IL-2 cytokines production in cultures of peripheral blood lymphocytes. Molecules 22(11):1789
Duprey SP, Boettiger D (1985) Developmental regulation of c-myb in normal myeloid progenitor cells. Proc Natl Acad Sci 82(20):6937–6941
Dwyer JM, Johnson C (1981) The use of concanavalin A to study the immunoregulation of human T cells. Clin Exp Immunol 46(2):237
Elisia I, Nakamura H. Lam V, Hofs E, Cederberg R, Cait J, Krystal G (2016) DMSO represses inflammatory cytokine production from human blood cells and reduces autoimmune arthritis. PLoS One 11(3):e0152538
Eckstein LA, Van Quill KR, Bui SK, Uusitalo MS, O’Brien JM (2005) Cyclosporin A inhibits calcineurin/nuclear factor of activated T-cells signaling and induces apoptosis in retinoblastoma cells. Invest Ophthalmol vis Sci 46(3):782–790
Emmel EA, Verweij CL, Durand DB, Higgins KM, Lacy E, Crabtree GR (1989) Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 246(4937):1617–1620
Fei C, Pemberton JG, Lillico DM, Zwozdesky MA, Stafford JL (2016) Biochemical and functional insights into the integrated regulation of innate immune cell responses by teleost leukocyte immune-type receptors. Biology 5(1):13
Fei C, Zwozdesky MA, Stafford JL (2020) A fish leukocyte immune-type receptor uses a novel intracytoplasmic tail networking mechanism to cross-inhibit the phagocytic response. Int J Mol Sci 21(14):5146
Frampton J (Ed.) (2004) MYB transcription factors: their role in growth, differentiation, and disease. Kluwer Academic
Goettsch C, Rauner M, Sinningen K, Helas S, Al-Fakhri N, Nemeth K, Hofbauer LC (2011) The osteoclast-associated receptor (OSCAR) is a novel receptor regulated by oxidized low-density lipoprotein in human endothelial cells. Endocrinology 152(12):4915–4926
Gonda TJ, Metcalf D (1984) Expression of myb, myc and fos proto-oncogenes during the differentiation of a murine myeloid leukaemia. Nature 310(5974):249–251
Grayfer L, Hodgkinson JW, Belosevic M (2011) Analysis of the antimicrobial responses of primary phagocytes of the goldfish (Carassius auratus L.) against Mycobacterium marinum. Dev Comp Immunol 35(11):1146–1158
Hanington PC, Barreda DR, Belosevic M (2006) A novel hematopoietic granulin induces proliferation of goldfish (Carassius auratus L.) macrophages. J Biol Chem 281(15), 9963–9970
Hanington PC, Hitchen SJ, Beamish LA, Belosevic M (2009) Macrophage colony stimulating factor (CSF-1) is a central growth factor of goldfish macrophages. Fish Shellfish Immunol 26(1):1–9
Hu Z, Gu X, Baraoidan K, Ibanez V, Sharma A, Kadkol S, Saunthararajah Y (2011) RUNX1 regulates corepressor interactions of PU. 1. Blood, Am J Hematol 117(24):6498–6508
Huang G, Zhang P, Hirai H, Elf S, Yan X, Chen Z, Tenen DG (2008) PU. 1 is a major downstream target of AML1 (RUNX1) in adult mouse hematopoiesis. Nat Genet 40(1):51–60
Huang HT, Su SC, Chiou TJ, Lin YH, Shih YC, Wu YX, Twu YC (2020) DNA methylation‐mediated Siglec‐7 regulation in natural killer cells via two 5′ promoter CpG sites. Immunology 160(1):38–51
Imperato MR, Cauchy P, Obier N, Bonifer C (2015) The RUNX1–PU. 1 axis in the control of hematopoiesis. Int J Hematol 101(4):319–329
Jansen CA, Cruijsen CW, de Ruiter T, Nanlohy N, Willems N, Janssens-Korpela PL, Meyaard L (2007) Regulated expression of the inhibitory receptor LAIR-1 on human peripheral T cells during T cell activation and differentiation. Eur J Immunol 37(4):914–924
Jones LO, Stafford JL (2019) Imaging flow cytometry and confocal microscopy-based examination of F-actin and phosphoinositide dynamics during leukocyte immune-type receptor-mediated phagocytic events. Dev Comp Immunol 92:199–211
Katzenback BA, Foroutanpay BV, Belosevic M (2013) Expressions of transcription factors in goldfish (Carassius auratus L.) macrophages and their progenitors. Dev Comp Immunol 41(2):230–239
Katzenback BA, Karpman M, Belosevic M (2011) Distribution and expression analysis of transcription factors in tissues and progenitor cell populations of the goldfish (Carassius auratus L.) in response to growth factors and pathogens. Mol Immunol 48(9–10):1224–1235
Katzenback BA, Katakura F, Belosevic M (2016) Goldfish (Carassius auratus L.) as a model system to study the growth factors, receptors and transcription factors that govern myelopoiesis in fish. Dev Comp Immunol 58:68–85
Konjević G, Vuletić A, Martinović KM, Džodić R (2017) The role of activating and inhibitory NK cell receptors in antitumor immune response. NK Cells 69–84
Kotwica-Mojzych K, Jodłowska-Jędrych B, Mojzych M (2021) CD200: CD200R interactions and their importance in immunoregulation. Int J Mol Sci 22(4):1602
Krmpotic A, Hasan M, Loewendorf A, Saulig T, Halenius A, Lenac T, Jonjic S (2005) NK cell activation through the NKG2D ligand MULT-1 is selectively prevented by the glycoprotein encoded by mouse cytomegalovirus gene m145. J Exp Med 201(2), 211–220
Lanier LL (2015) NKG2D receptor and its ligands in host defense. Cancer Immunol Res 3(6):575–582
Lei HY, Chang CP (2009) Lectin of Concanavalin A as an anti-hepatoma therapeutic agent. J Biomed Sci 16(1):1–12
Lillico DM, Pemberton JG, Stafford JL (2016) Trypsin differentially modulates the surface expression and function of channel catfish leukocyte immune-type receptors. Dev Comp Immunol 65:231–244
Lillico DM, Pemberton JG, Stafford JL (2018) Selective regulation of cytoskeletal dynamics and filopodia formation by teleost leukocyte immune-type receptors differentially contributes to target capture during the phagocytic process. Front Immunol 9:1144
Luckasen JR, White JG, Kersey JH (1974) Mitogenic properties of a calcium ionophore, A23187. Proc Natl Acad Sci 71(12):5088–5090
Mewes J, Verheijen K, Montgomery BC, Stafford JL (2009) Stimulatory catfish leukocyte immune-type receptors (IpLITRs) demonstrate a unique ability to associate with adaptor signaling proteins and participate in the formation of homo-and heterodimers. Mol Immunol 47(2–3):318–331
Meloni S, Zarletti G, Benedetti S, Randelli E, Buonocore F, Scapigliati G (2006) Cellular activities during a mixed leucocyte reaction in the teleost sea bass Dicentrarchus labrax. Fish Shellfish Immunol 20(5):739–749
Miach PJ (1986) Cyclosporin A in organ transplantation. Med J Aust 145(3–4):146–150
Miller NW, Deuter A, Clem LW (1986) Phylogeny of lymphocyte heterogeneity: the cellular requirements for the mixed leucocyte reaction with channel catfish. Immunology 59(1):123
Montgomery BC, Cortes HD, Burshtyn DN, Stafford JL (2012) Channel catfish leukocyte immune-type receptor mediated inhibition of cellular cytotoxicity is facilitated by SHP-1-dependent and-independent mechanisms. Dev Comp Immunol 37(1):151–163
Nakajima H, Asai A, Okada A, Ping L, Hamajima F, Sata T, Isobe K (2003) Transcriptional regulation of ILT family receptors. J Immunol 171(12):6611–6620
Neumann NF, Barreda D, Belosevic M (1998) Production of a macrophage growth factor (s) by a goldfish macrophage cell line and macrophages derived from goldfish kidney leukocytes. Dev Comp Immunol 22(4):417–432
Neumann NF, Barreda DR, Belosevic M (2000) Generation and functional analysis of distinct macrophage sub-populations from goldfish (Carassius auratus L.) kidney leukocyte cultures. Fish Shellfish Immunol 10(1):1–20
Neumann NF, Fagan D, Belosevic M (1995) Macrophage activating factor (s) secreted by mitogen stimulated goldfish kidney leukocytes synergize with bacterial lipopolysaccharide to induce nitric oxide production in teleost macrophages. Dev Comp Immunol 19(6):473–482
Paludan SR, Pradeu T, Masters SL, Mogensen TH (2021) Constitutive immune mechanisms: mediators of host defence and immune regulation. Nat Rev Immunol 21(3):137–150
Poggi A, Tomasello E, Ferrero E, Zocchi MR, Moretta L (1998) p40/LAIR-1 regulates the differentiation of peripheral blood precursors to dendritic cells induced by granulocyte-monocyte colony-stimulating factor. Eur J Immunol 28(7):2086–2091
Robinson PJ (1992) Differential stimulation of protein kinase C activity by phorbol ester or calcium/phosphatidylserine in vitro and in intact synaptosomes. J Biol Chem 267(30):21637–21644
Soza-Ried C, Hess I, Netuschil N, Schorpp M, Boehm T (2010) Essential role of c-myb in definitive hematopoiesis is evolutionarily conserved. Proc Natl Acad Sci 107(40):17304–17308
Stafford JL, Bengtén E, Du Pasquier L, McIntosh RD, Quiniou SM, Clem LW, Wilson M (2006) A novel family of diversified immunoregulatory receptors in teleosts is homologous to both mammalian Fc receptors and molecules encoded within the leukocyte receptor complex. Immunogenetics 58(9):758–773
Stafford JL, Bengtén E, Du Pasquier L, Miller NW, Wilson M (2007) Channel catfish leukocyte immune-type receptors contain a putative MHC class I binding site. Immunogenetics 59(1):77–91
Stafford JL, Galvez F, Goss GG, Belosevic M (2002) Induction of nitric oxide and respiratory burst response in activated goldfish macrophages requires potassium channel activity. Dev Comp Immunol 26(5):445–459
Studzinski GP, Brelvi ZS (1987) Changes in proto-oncogene expression associated with reversal of macrophage-like differentiation of HL 60 cells. J Natl Cancer Inst 79(1):67–76
Tahara E, Kadara H, Lacroix L, Lotan D, Lotan R (2009) Activation of protein kinase C by phorbol 12-myristate 13-acetate suppresses the growth of lung cancer cells through KLF6 induction. Cancer Biol Ther 8(9):801–807
Tedla N, Lee CW, Borges L, Geczy CL, Arm JP (2008) Differential expression of leukocyte immunoglobulin-like receptors on cord blood-derived human mast cell progenitors and mature mast cells. J Leukoc Biol 83(2):334–343
Tomita M, Reinhold MI, Molkentin JD, Naski MC (2002) Calcineurin and NFAT4 induce chondrogenesis. J Biol Chem 277(44):42214–42218
Thomson AW (1992) The effects of cyclosporin A on non-T cell components of the immune system. J Autoimmun 5:167–176
Verbrugge A, De Ruiter T, Geest C, Coffer PJ, Meyaard L (2006) Differential expression of leukocyte-associated Ig-like receptor-1 during neutrophil differentiation and activation. J Leukoc Biol 79(4):828–836
Wang J, Belosevic M, Stafford JL (2020) Identification of goldfish (Carassius auratus L.) leukocyte immune-type receptors shows alternative splicing as a potential mechanism for receptor diversification. Mol Immunol 125:83–94
Wang J, Belosevic M, Stafford JL (2021) Identification of distinct LRC-and Fc receptor complex-like chromosomal regions in fish supports that teleost leukocyte immune-type receptors are distant relatives of mammalian Fc receptor-like molecules. Immunogenetics 73(1):93–109
Young NT, Waller EC, Patel R, Roghanian A, Austyn JM, Trowsdale J (2008) The inhibitory receptor LILRB1 modulates the differentiation and regulatory potential of human dendritic cells. Blood, the Journal of the American Society of Hematology 111(6):3090–3096
Zhang JM, An J (2007) Cytokines, inflammation, and pain. Int Anesthesiol Clin 45(2):27
Zwozdesky MA, Fei C, Lillico DM, Stafford JL (2017) Imaging flow cytometry and GST pulldown assays provide new insights into channel catfish leukocyte immune-type receptor-mediated phagocytic pathways. Dev Comp Immunol 67:126–138
Funding
This work was supported by grants from the Natural Sciences and Engineering Council of Canada (NSERC) awarded to Miodrag Belosevic (Grant no. RGPIN-2014–06395) and James L. Stafford (Grant no. RGPIN-2017–05442). Jiahui Wang was supported by a University of Alberta recruitment scholarship, a research assistantship, and a teaching assistantship from the Department of Biological Sciences of the University of Alberta.
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Wang, J., Soliman, A.M., Norlin, J. et al. Expression analysis of Carassius auratus-leukocyte-immune-type receptors (CaLITRs) during goldfish kidney macrophage development and in activated kidney leukocyte cultures. Immunogenetics 75, 171–189 (2023). https://doi.org/10.1007/s00251-023-01298-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-023-01298-5