this is the slide I used in the immunology class

1. AUTOIMMUNITY&FOOD Are we missing something? PUMC2006 陈朗

2. Autoimmune diseases: a brief introduction Systemic Lupus(SLE) Sclerodermia Vasculitis Organ-specific Type 1 diabetes endocrine pancreas Asthma lung Rhumatoid arthritis joints Myositis muscle Thyroiditis (Graves, Hashimoto) thyroid APECED endocrine glands Multiple sclerosis nervous tissue Anemia, thrombopenia, neutropenia blood cells Psoriasis, eczema skin Gastritis stomach Colitis (Crohn, UC) colon Uveitis eye …..

3. Many autoimmune diseases are difficult or impossible to cure for the obvious reason that the focus of the immune response – self antigens - cannot be eliminatedThe ultimate mechanism involve a failure of tolerance and the accumulation of irreversible damage in the target tissues

4. Unclear mechenisms

5. Epidemiology[2] Diseases affecting young adults Female > male Triggering and / or evolution often influenced by infectious diseases, pregnancy, traumatisms Familial trends North-South gradient Higher prevalence in nordic countries[1,2]

6. Epidemiology Environmental factors(Food & nutrition) Genetic factors Psychological factors ……

7. Evidences suggest that:

8. Evidences suggest that:

10. Evidences suggest that[18-23]: Vitamin D and vitamin D receptor(VDR) deficiency resulted in accelerated IBD. Vitamin D decreases the risk of RA And that of type 1 diabetes Fat increases the risk of hemolytic anemia Gluten(wheat) increases the risk of coeliac disease(CD) Food restriction lowers the risk of SLE, and vitamin A can help treat it ……

11. Autoimmune diseases: a brief introduction Systemic Lupus(SLE) Sclerodermia Vasculitis Organ-specific Type 1 diabetes endocrine pancreas Asthma lung Rhumatoid arthritis joints Myositis muscle Thyroiditis (Graves, Hashimoto) thyroid APECED endocrine glands Multiple sclerosis nervous tissue Anemia, thrombopenia, neutropenia blood cells Psoriasis, eczema skin Gastritis stomach Colitis (Crohn, UC) colon Uveitis eye …..

12. Why? Common Severity most studied & resent achievement Significance The type of food is common! Good potential in prevention & treatment

13. Food autoimmune?! Molecular mimicry T cell regulation Other possible mechanisms

14. MS &vitamin D[1,12-17] Nutrition Exercise Stress Social

15. vitamin D

16. VDR Gene regulator Many tissues Skin Bone Activated monocytesand B and T lymphocytes Central nervous system (CNS) Muscles Gonads Intestine Microglia

17. Epidemiological conclusions 25(OH)D3 level : high in summer, low in winter MS severity: spring Latitude , past exposure to sun and the serum level of vitamin D influence the risk of MS HypovitaminosisD?

19. Experimental and immunological studies Vitamin D Protective Curative Immunomodulatory effect Anti-inflammatory effect reducing macrophages increasing TGF- β1 and IL-4 Induction of apoptosis a protective effect on myelin by activating oligodendrocytes

20. Immunomodulatory effectof vitamin D VDR & gene transcription Th1 development Th2 and Treg restoration Cytokines: Th1:IFN-γ,IL-2,TNF-α Th2:IL-4 & IL-5 Vitamin D In Th1 cells: IL-12:Th1 number & function JAK-STAT signaling pathway

22. Immunomodulatory effectof vitamin D In Th2cells Number : unknown IL-10:Production of IL-4 Overall Autoimmunity(EAE) Reduction of severity

24. Prevention & treatment Vitamin D has a preventive effect on MS The treatment of vit D is currently under clinical trial phase 1, which has gained positive results

25. Food containing vitamin D:for the normal majority

26. Managing MS:are we forgetting something? conventional medicines only modestly effective may have significant side-effects Diet(low saturated fat, vitamin D) stress management Exercise the best of medical management

27. Unclear mechenisms

28. Type 1 diabetes &cow’s milk[1,3-7] Bad gene(s) + Environmental factors =Danger!

29. Importance?

31. Possible machenisms Molecular mimicry

32. Who are gonna be happy?

33. References T. COLIN CAMPBELL, PHD and THOMAS M. CAMPBELL II, “The China Study The Most Comprehensive Study of Nutrition Ever Conducted”, BENBELLA BOOKS,2006 Arthur Rabson，”Really Essential Medical Immunology”，blackwell publishing,2005 Savilahti E, Akerblom HK, Tainio V-M, et al. "Children with newly diagnosed insulin dependent diabetes mellitus have increased levels of cow's milk antibodies." Diabetes Res. 7 (1988): 137-140.Asdfasdf Akerblom HK, Vaarala 0, Hyoty H, et al. "Environmental factors in the etiology of Type 1 diabetes." Am. ]. Med. Genet. (Semin. Med. Genet.) 115 (2002): 18-29. KostrabaJN, Cruickshanks KJ, Lawler-Heavner J, et al. "Early exposure to cow's milk and solid foods in infancy; genetic predisposition, and risk of lODM." Diabetes 42 (1993): 288-295. Gerstein He. "Cow's milk exposure and Type 1 diabetes mellitus: a critical overview of the clinical literature." Diabetes Care 17 (1994): 13-19. Virtanen SM, Laara E, Hypponen E, et al. "Cow's milk consumption, HLA-DQB1 genotype,and Type 1 diabetes." Diabetes 49 (2000): 912-917. Charles Pierrot-Deseilligny, ”Clinical implications of a possible role of vitamin D in multiple sclerosis”, J Neurol (2009) 256:1468–1479

34. References Michael F Holick, ”Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease”, Am J ClinNutr2004;80(suppl) George A Jelinek，” Managing multiple sclerosis in primary care: are we forgetting something?”, Quality in Primary Care 2009;17:55–61 A. Payne. "Nutrition and diet in the clinical management of multiple sclerosis”,2001 J Hum Nutr Dietet, 14, pp. 349±357 GladsonMuthian. "1,25 Dihydroxyvitamin-D3 Modulates JAK–STAT pathway in IL-12/IFNc Axis Leading to Th1 Response in Experimental Allergic Encephalomyelitis." Journal of Neuroscience Research 83:1299–1309 (2006) Frank Mattner1, Simona,“Inhibitionof Th1 development and treatment of chronic-relapsing experimental allergic encephalomyelitis by a non-hypercalcemic analogue of 1,25-dihydroxyvitamin D3." Eur. J. Immunol. 2000. 30: 498–508 MARGHERITA T. CANTORNA. "Mounting Evidence for Vitamin D as an Environmental Factor Affecting Autoimmune Disease Prevalence”, Exp Biol Med 229:1136–1142, 2004 P. Szodoray. "The Complex Role of Vitamin D in Autoimmune Diseases." 2008 Blackwell Publishing Ltd. Scandinavian Journal of Immunology 68, 261–269 Sarah A. Stechschulte, ” Vitamin D: Bone and Beyond, Rationale and Recommendations for Supplementation”, The American Journal of Medicine, Vol 122, No 9, September 2009

35. References Margherita T Cantorna, Yan Zhu, Monica Froicu, and AnjaWittke, ” Vitamin D status, 1,25-dihydroxyvitamin D3, and the immune system”, Am J ClinNutr 2004;80(suppl):1717S–20S MASAHIKO ÃoeRAO， Food Restriction Inhibits an Autoimmune Disease Resembling Systemic Lupus Erythematosus in (NZB x NZW) Fl Mice”, J. Nutr. 125: 2316-2324, 1995. Tom Patavino ," Natural Medicine and Nutritional Therapy as an Alternative Treatment in Systemic Lupus Erythematosus”, Alternative Medicine Review Volume 6, Number 5 2001 J. HOMSY, W. J. W. MORROW & J. A. LEVY. " Nutrition and autoimmunity: a review." Clin. exp. Immunol. (1986), 65, 473-488 Abraham R Eliakim,“Nutritional status and nutritional therapy in inflammatory bowel diseases." World J Gastroenterol 2009 June 7; 15(21): 2570-2578 Gabriel Fernandes. " Progress in nutritional immunology Immunol Res (2008) 40:244–261 GABRIEL FERNANDES. " Influence of diet on vascular lesions in autoimmune-prone B/W mice”, Proc. Nati Acad. Sci. USA 80 (1983)

36. Thank you very much! PUMC2006 陈朗