Comparing genetic pathways variation of immunoinhibitory receptor LAIR-1 in murine vs human internal organs
BMC Bioinformatics volume 15, Article number: P9 (2014)
Recent evidence suggests that leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) may play an important role in down-regulating immune activities upon collagen binding , and its defective expression or dysfunction is clinically associated with some autoimmune diseases [2–5], cancer [6–8] and viral infection [9–12]. The human genome encodes the counterpart to LAIR-1, soluble protein LAIR-2 , which also binds collagen and can interfere with LAIR-1/collagen interactions . However, LAIR-2 has no homologue in mouse or rat . To clarify the extrapolative credibility of a murine model to human disease, we compared LAIR-1 genetic pathways in internal organs of the two species.
Materials and methods
We used the GeneNetwork software developed by the University of Tennessee, and six eligible datasets of normal liver, lung, and brain tissue from the linked database .
The top genes shared by mouse and human on the basis of Pearson correlation, were picked for plotting network graphs in GeneNetwork. An r absolute value >0.50 was considered to indicate connection line threshold.
Significant variation in LAIR-1 genetic pathways was found in mouse vs human internal organs
The top 50 mouse genes by LAIR-1’s Pearson correlation were employed to search for the same genes in corresponding human tissue throughout relevant databases. There were 33 common genes found in liver, 32 in lung, and 31 in brain. The network node of LAIR-1 has a more robust connection for mouse than for human, and no common genes except for LAIR-1 were shared by liver, lung and brain in mice or humans. These observations can be confirmed in liver with the common genes of the top 100 human and top 100 mouse LAIR-1 relevant genes.
Genetic interaction of human LAIR-1 with LAIR-2 in vivo rarely occurred
The interaction of LAIR-2 with LAIR-1 only occurred in the top 200 genes for lung tissue with a positive coefficient of 0.426, and in the top 300 genes for brain tissue with a negative coefficient of -0.242, but not for liver tissue, according to Pearson correlation distance and intensity.
LAIR-1 genetic pathways have noteworthy species difference and tissue specificity, which may cause overestimation if using mouse experimental data to evaluate human conditions. Moreover, human LAIR-1 and LAIR-2 actually get the rare opportunity to interact in vivo, implying that species difference in regard to LAIR-1 genetic pathways could not be primarily attributed to the existence of human LAIR-2.
Meyaard L, Hurenkamp J, Clevers H, Lanier LL, Phillips JH: Leukocyte-associated Ig-like receptor-1 functions as an inhibitory receptor on cytotoxic T cells. J Immunol. 1999, 162: 5800-5804.
Olde Nordkamp MJ, van Roon JA, Douwes M, de Ruiter T, Urbanus RT, Meyaard L: Enhanced secretion of leukocyte-associated immunoglobulin-like receptor 2 (LAIR-2) and soluble LAIR-1 in rheumatoid arthritis: LAIR-2 is a more efficient antagonist of the LAIR-1-collagen inhibitory interaction than is soluble LAIR-1. Arthritis Rheum. 2011, 63: 3749-3757. 10.1002/art.30612.
Colombo BM, Canevali P, Magnani O, Rossi E, Puppo F, Zocchi MR, Poggi A: Defective expression and function of the leukocyte associated Ig-like receptor 1 in B lymphocytes from systemic lupus erythematosus patients. PLoS One. 2012, 7: e31903-10.1371/journal.pone.0031903.
Simone R, Pesce G, Antola P, Merlo DF, Bagnasco M, Saverino D: Serum LAIR-2 is increased in autoimmune thyroid diseases. PLoS One. 2013, 8: e63282-10.1371/journal.pone.0063282.
Son M, Santiago-Schwarz F, Al-Abed Y, Diamond B: C1q limits dendritic cell differentiation and activation by engaging LAIR-1. Proc Natl Acad Sci USA. 2012, 109: E3160-E3167. 10.1073/pnas.1212753109.
Zocchi MR, Pellegatta F, Pierri I, Gobbi M, Poggi A: Leukocyte-associated Ig-like receptor-1 prevents granulocyte-monocyte colony stimulating factor-dependent proliferation and Akt1/PKB alpha activation in primary acute myeloid leukemia cells. Eur J Immunol. 2001, 31: 3667-3675. 10.1002/1521-4141(200112)31:12<3667::AID-IMMU3667>3.0.CO;2-G.
Poggi A, Catellani S, Bruzzone A, Caligaris-Cappio F, Gobbi M, Zocchi MR: Lack of the leukocyte-associated Ig-like receptor-1 expression in high-risk chronic lymphocytic leukaemia results in the absence of a negative signal regulating kinase activation and cell division. Leukemia. 2008, 22: 980-988. 10.1038/leu.2008.21.
Rygiel TP, Stolte EH, de Ruiter T, van de Weijer ML, Meyaard L: Tumor-expressed collagens can modulate immune cell function through the inhibitory collagen receptor LAIR-1. Mol Immunol. 2011, 49: 402-406. 10.1016/j.molimm.2011.09.006.
Aoukaty A, Lee IF, Wu J, Tan R: Chronic active Epstein-Barr virus infection associated with low expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on natural killer cells. J Clin Immunol. 2003, 23: 141-145. 10.1023/A:1022580929226.
De Milito A, Nilsson A, Titanji K, Thorstensson R, Reizenstein E, Narita M, Grutzmeier S, Sönnerborg A, Chiodi F: Mechanisms of hypergammaglobulinemia and impaired antigen-specific humoral immunity in HIV-1 infection. Blood. 2004, 103: 2180-2186. 10.1182/blood-2003-07-2375.
Titanji K, Chiodi F, Bellocco R, Schepis D, Osorio L, Tassandin C, Tambussi G, Grutzmeier S, Lopalco L, De Milito A: Primary HIV-1 infection sets the stage for important B lymphocyte dysfunctions. AIDS. 2005, 19: 1947-1955. 10.1097/01.aids.0000191231.54170.89.
Kennedy PT, Sandalova E, Jo J, Gill U, Ushiro-Lumb I, Tan AT, Naik S, Foster GR, Bertoletti A: Preserved T-cell function in children and young adults with immune-tolerant chronic hepatitis B. Gastroenterology. 2012, 143: 637-645. 10.1053/j.gastro.2012.06.009.
Lebbink RJ, van den Berg MC, de Ruiter T, Raynal N, van Roon JA, Lenting PJ, Jin B, Meyaard L: The soluble leukocyte-associated Ig-like receptor (LAIR)-2 antagonizes the collagen/LAIR-1 inhibitory immune interaction. J Immunol. 2008, 180: 1662-1669. 10.4049/jimmunol.180.3.1662.
Lenting PJ, Westerlaken GH, Denis CV, Akkerman JW, Meyaard L: Efficient inhibition of collagen-induced platelet activation and adhesion by LAIR-2, a soluble Ig-like receptor family member. PLoS One. 2010, 5: e12174-10.1371/journal.pone.0012174.
We are grateful to Dr. Robert Williams for his generosity in providing data in the GeneNetwork for this analysis.
About this article
Cite this article
Sun, S., Jiao, Y., Wei, W. et al. Comparing genetic pathways variation of immunoinhibitory receptor LAIR-1 in murine vs human internal organs. BMC Bioinformatics 15 (Suppl 10), P9 (2014). https://doi.org/10.1186/1471-2105-15-S10-P9