DOI QR코드

DOI QR Code

Evaluation of Mucosal Immunity in BTBR T+tf/J Mice Resembling Autism Spectrum Disorder

자폐증 유사증상 발현 마우스의 점액 면역에 대한 연구

  • Hwang, So Ryeon (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Jo, Ji Hoon (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Shin, Kyeong Min (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Jang, Yun Young (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Kim, Ji Youn (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Yeo, Kyeong Uk (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health) ;
  • Kim, Hyoung Ah (The Catholic University of Korea, College of Medicine, Dept. Preventive Medicine) ;
  • Heo, Yong (Catholic University of Daegu, College of Natural Sciences, Dept. Occupational Health)
  • 황소련 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 조지훈 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 신경민 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 장윤영 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 김지연 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 여경욱 (대구가톨릭대학교 자연대학 산업보건학과) ;
  • 김형아 (가톨릭대학교 의과대학 예방의학교실) ;
  • 허용 (대구가톨릭대학교 자연대학 산업보건학과)
  • Received : 2012.11.05
  • Accepted : 2012.11.28
  • Published : 2012.12.31

Abstract

Objectives: This study was undertaken in order to evaluate a potential mechanism involved in gastro-intestinal problems observed in autistic subjects and uses an animal model of autism investigation. Methods: BTBR T+tf/J, a mouse strain with typical socio-behavioral characteristics of autistic subjects and FVB mice with highly social behaviors as the control strain were used. Both genders of mice aged three weeks and six months were used from four separate litters for each strain. Serum was prepared following cardiac puncture, and mesenteric lymph nodes were collected for in vitro stimulation and enumeration of major immune cell proportion. Results: The level of serum IgA was significantly enhanced in six-month-old BTBR mice compared with three-week-old BTBR, which was not observed with the FVB control mice. The serum IgE level was also higher among BTBR mice than among age-sex matched FVB mice, respectively. Considering the ratio of interleukin-4 vs interferon-gamma production from mesenteric lymph node T cells, skewedness toward type-2 reactivities was observed. In addition, the proportion of B cells in mesenteric lymph nodes was significantly higher in BTBR mice than in FVB mice. Conclusion: Upregulation of mucosal immunity related with enhanced type-2 immune reactivity observed in BTBR mice could be involved with the etiology of gastro-intestinal abnormalities in autism.

Keywords

References

  1. Becker KG. Autism, asthma, inflammation, and the hygiene hypothesis. Med Hypotheses. 2007; 69: 731-740. https://doi.org/10.1016/j.mehy.2007.02.019
  2. Geschwind DH. Advances in autism. Annu Rev Med. 2009; 60: 367-380. https://doi.org/10.1146/annurev.med.60.053107.121225
  3. Grigorenko EL. Pathogenesis of autism: a patchwork of genetic causes. Future Neurol. 2009; 4: 591-599. https://doi.org/10.2217/fnl.09.29
  4. Rosenberg RE, Law JK, Yenokyan G, McGready J, Kaufman WE, Law PA. Characteristics and concordance of autism spectrum disorders among 277 twin pairs. Arch Pediatr Adolesc Med. 2009; 163: 907- 914. https://doi.org/10.1001/archpediatrics.2009.98
  5. CDC. Prevalence of autism spectrum disorders - Autism and Developmental Disabilities Monitoring Network, United States, 2006. MMWR Surveill Summ. 2009; 58: 1-20.
  6. Kim YS, Leventhal BL, Koh YJ, Fombonne E, Laska E, Lim EC, et al. Prevalence of autism spectrum disorders in a total population sample. Am J Psychiatry. 2011; 168: 904-912. https://doi.org/10.1176/appi.ajp.2011.10101532
  7. Blaylock RL. A possible central mechanism in autism spectrum disorders, part 1. Altern Ther Health Med. 2008; 14(6): 46-53.
  8. Blaylock RL. A possible central mechanism in autism spectrum disorders, part 2: immunoexcitotoxicity. Altern Ther Health Med. 2009; 15(1): 60- 67.
  9. Blaylock RL. A possible central mechanism in autism spectrum disorders, part 3: the role of excitotoxin food additives and the synergistic effects of other environmental toxins. Altern Ther Health Med. 2009; 15(2): 56-60.
  10. Stigler KA, Sweeten TL, Posey DJ, McDougle CJ. Autism and immune factors: a comprehensive review. Res Autism Spectr Disord. 2009; 3: 840- 860. https://doi.org/10.1016/j.rasd.2009.01.007
  11. Moy SS, Nadler JJ, Young NB, Perez A, Holloway LP, Barbaro RP, et al. Mouse behavioral tasks relevant to autism: phenotypes of 10 inbred strains. Behav. Brain Res. 2007; 176: 4-20. https://doi.org/10.1016/j.bbr.2006.07.030
  12. Bolivar VJ, Walters SR, Phoenix JL. Assessing autism-like behavior in mice: variations in social interactions among inbred strains. Behav. Brain Res. 2007; 176: 21-26. https://doi.org/10.1016/j.bbr.2006.09.007
  13. McFarlane HG, Kusek GK, Yang M, Phoenix JL, Bolivar VJ, Crawley JN. Autism-like behavioral phenotypes in BTBR T+tf/J mice. Genes Brain Behav. 2008; 7: 152-163. https://doi.org/10.1111/j.1601-183X.2007.00330.x
  14. Heo Y, Zhang Y, Gao D, Miller VM, Lawrence DA. Aberrant immune responses in a mouse with behavioral disorders. PLoS One. 2011; 6(7): e20912. https://doi.org/10.1371/journal.pone.0020912
  15. Park H-S, Heo Y-J, Byun J-A, Heo Y. Immunotoxicological evaluation of pollen intake using mice model. J Environ Health Sci. 2005; 31(4): 287-293.
  16. Lee S-H, Baek S-J, Kim H-A, Heo Y. 2,4-dinitrochrlobenzene- induced atopic dermatitis like immune alteration in mice. J Toxicol Pub Health. 2006; 22(4): 357-364.
  17. Kim S-N, Kim Y-C, Kim H-A, Heo Y. A potential mechanism of 2,4-dinitrochlorobenzene-mediated immune alterations resembling human atopic dermatitis in mice. Quant Bio-Sci. 2011; 30(2): 85-90.
  18. Heo Y, Saxon A, Hankinson O. Effect of diesel exhaust particles and their components on the allergen- specific IgE and IgG1 response in mice. Toxicology, 2001; 159: 143-158. https://doi.org/10.1016/S0300-483X(00)00418-2
  19. Gans H, De Hovitz R, Forghani B, Beeler J, Maldonado Y, Arvin AM. Measles and mumps vaccination as a model to investigate the developing immune system: passive and active immunity during the first year of life. Vaccine. 2003; 21: 3398- 3405. https://doi.org/10.1016/S0264-410X(03)00341-4
  20. Ashwood P, Van de Water J. A review of autism and the immune response. Clin Develop Immunol. 2004; 11(2): 165-174. https://doi.org/10.1080/10446670410001722096
  21. Torrente F, Ashwood P, Day R, Machado N, Furlano RI, Anthony A, et al. Small intestinal enteropathy with epithelial IgG and complement deposition in children with regressive autism. Mol Psychiatry. 2002; 7: 375-382. https://doi.org/10.1038/sj.mp.4001077
  22. Sutherland DB, Fagarasan S. IgA synthesis: a form of functional immune adaptation extending beyond gut. Curr Opin Immunol. 2012; 24: 261-268. https://doi.org/10.1016/j.coi.2012.03.005
  23. Reichelt KL, Landmark J. Specific IgA antibody increases in schizophrenia. Biol Psychiatry. 1995; 37: 410-413. https://doi.org/10.1016/0006-3223(94)00176-4
  24. Maes M, Mihaylova I, Leunis JC. Increased serum IgA and IgM against LPS of enterobacteria in chronic fatigue syndrome (CFS): indication for the involvement og gram-negative enterobacteria in the etiology of CFS and for the presence of an increased gut-intestinal permeability. J Affective Disorders. 2007; 99: 237-240. https://doi.org/10.1016/j.jad.2006.08.021
  25. Edelson BT, Unanue ER. Immunity to listeria infection. Curr Opin Immunol. 2000; 12: 425-431. https://doi.org/10.1016/S0952-7915(00)00112-6