Iranian Journal of Allergy, Asthma and Immunology 2017. 16(2):159-168.

Eliciting Th1 Immune Response Using Casein- (Alpha S1) loaded Dendritic Cells
Saeed Daneshmandi, Maryam Nourizadeh, Zahra Pourpak, Ali Akbar Pourfathollah


Allergen-specific immunotherapy (AIT) has been recently considered as an alternative approach to ameliorate the symptoms of allergen exposure and improvement the patients’ quality of life. Dendritic cells (DC) in the forms of tolerogenic or Th1-induced cells have been investigated in several studies as one of the promising approaches of AIT in allergic diseases. The aim of this study was to evaluate the potency of casein-loaded DCs in eliciting the Th1 immune responses in Balb/c mice as a potential therapeutic approach in allergic condition. Immature bone marrow-derived DCs were loaded with casein (protein or mRNA) or green fluorescent protein (GFP) mRNA. DCs were evaluated based on the expression of specific markers and production of proinflammatory cytokines. Proliferation and cytokine production of lymph node lymphocytes and splenocytes were measured in DC-injected mice. Expression of DC markers in all groups was significantly higher than immature DCs, but lower than LPS-activated DCs. Despite an increase in TNF-α and IL-12, IL-6 was decreased in casein-DC treatments. Caseinloaded DCs could induce proliferation in lymphocytes and stimulate them to produce higher amounts of IFN-γ and in some extent IL-10 and TGF-β, while they could not stimulate IL-4 secretion. Casein-loaded DCs could partially elicit the Th1 responses; this would be a promising approach to use them as an allergic protective way for applying immune cell therapy in cow’s milk allergy.


Casein; Dendritic cells; Milk hypersensitivities

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1.   Tsabouri   S,   Douros   K,   Priftis   KN.   Cow's   milk allergenicity. Endocr Metab Immune Disord Drug Targets 2014; 14(1):16-26.

2.   Coscia A, Orru S, Di Nicola P, Giuliani F, Rovelli I, Peila C, et al. Cow's milk proteins in human milk. J Biol Regul Homeost Agents 2012; 26(3 Suppl):39-42.

3.   Nakajima-Adachi  H,  Hachimura  S,  Ise  W,  Honma  K,Nishiwaki S, Hirota M, et al. Determinant analysis of IgE and IgG4 antibodies and T cells specific for bovine alpha(s)1-casein from the same patients allergic to cow's milk: existence of alpha(s)1-casein-specific B cells and T cells characteristic in cow's-milk allergy. J Allergy Clin Immunol 1998; 101(5):660-71.

4. Matsuoka T, Shamji MH, Durham SR. Allergen immunotherapy   and   tolerance.   Allergol   Int    2013;62(4):403-13.

5.  Akdis CA, Akdis M. Mechanisms of allergen-specific immunotherapy   and   immune   tolerance   to   allergens. World Allergy Organ J 2015; 8(1):17.

6.   Cavkaytar  O,  Akdis  CA,   Akdis  M.   Modulation   of immune responses by immunotherapy in allergic diseases. Curr Opin Pharmacol 2014; 17:30-7.

7.   Bidad K, Nicknam MH, Farid R. A review of allergy and allergen specific immunotherapy. Iran J Allergy Asthma Immunol 2011; 10(1):1-9.

8.   Salazar F, Ghaemmaghami AM. Allergen recognition by innate  immune   cells:   critical   role   of  dendritic   and epithelial cells. Front Immunol 2013; 4:356.

9.   Escobar A, Aguirre A, Guzman MA, Gonzalez R, Catalan D, Acuna-Castillo  C, et al.  Tolerogenic dendritic  cells derived from donors with natural rubber latex allergy modulate allergen-specific T-cell responses and IgE production. PLoS One 2014; 9(1):e85930.

10. Frischmeyer-Guerrerio  PA,  Keet  CA,  Guerrerio  AL, Chichester KL, Bieneman AP, Hamilton RG, et al. Modulation of dendritic cell innate and adaptive immune functions by oral and sublingual immunotherapy. Clin Immunol 2014; 155(1):47-59.

11. Wu L, Liu YJ. Development of dendritic-cell lineages.Immunity 2007; 26(6):741-50.

12. Yang X, Gao X. Role of dendritic cells: a step forward for the hygiene hypothesis. Cell Mol Immunol 2011; 8(1):12-8.

13. Klostermann B, Bellinghausen I, Bottcher I, Petersen A, Becker WM, Knop J, et al. Modification of the human allergic immune response by allergen-DNA-transfected dendritic cells in  vitro. J Allergy Clin Immunol 2004;113(2):327-33.

14. Ashjaei K, Bublin M, Smole U, Lengger N, Hafner C, Breiteneder  H,  et  al.  Differential  T-helper  cell polarization after allergen-specific stimulation of autologous dendritic cells in polysensitized allergic patients. Int Arch Allergy Immunol 2015; 166(2):97-106.

15. Suzuki M, Zheng X, Zhang X, Zhang ZX, Ichim TE, Sun H,  et  al.  A  novel  allergen-specific  therapy  for  allergy using CD40-silenced dendritic cells. J Allergy Clin Immunol 2010; 125(3):737-43.

16. Daneshmandi S, Pourfathollah AA, Karimi MH, Emadi- Baygi M. PDL-1/PDL-2 blockade in mice dendritic cells by RNAi techniques to induce antitumor immunity. Immunotherapy 2015; 7(11):1145-58.

17. Canonica GW, Cox L, Pawankar R, Baena-Cagnani CE, Blaiss M,  Bonini  S, et  al.  Sublingual  immunotherapy: World Allergy Organization position paper 2013 update. World Allergy Organ J 2014; 7(1):6.

18. DuBuske  LM.  Appropriate  and  inappropriate  use  of immunotherapy.  Ann  Allergy  Asthma  Immunol  2001;87(1 Suppl 1):56-67.

19. Taher YA, Henricks PA, van Oosterhout AJ. Allergen- specific subcutaneous immunotherapy in allergic asthma: immunologic  mechanisms  and  improvement.  Libyan  J Med 2010; 5.

20. Liu Z, Jiang Y, Li C. Design of a ProDer f 1 vaccine delivered by the MHC class II pathway of antigen presentation and analysis of the effectiveness for specific immunotherapy. Int J Clin Exp Pathol 2014; 7(8):4636-44.

21. Suzuki M, Zheng X, Zhang X, Li M, Vladau C, Ichim TE,  et  al.  Novel  vaccination  for  allergy  through  gene silencing of CD40 using small interfering RNA. J Immunol 2008; 180(12):8461-9.

22. Jankovic  D,  Kullberg  MC,  Feng  CG,  Goldszmid  RS, Collazo CM, Wilson M, et al. Conventional T- bet(+)Foxp3(-) Th1 cells are the major source of host- protective regulatory IL-10 during intracellular protozoan infection. J Exp Med 2007; 204(2):273-83.

23. Stripecke R, Carmen Villacres M, Skelton D, Satake N, Halene S, Kohn D. Immune response to green fluorescent protein: implications for gene therapy. Gene Ther 1999;6(7):1305-12.

24. Dioszeghy  V,  Mondoulet  L,  Dhelft  V,  Ligouis  M, Puteaux E, Benhamou PH, et al. Epicutaneous immunotherapy results in rapid allergen uptake by dendritic cells through intact skin and downregulates the allergen-specific response in sensitized mice. J Immunol 2011; 186(10):5629-37.

25. Jo J, Garssen J, Knippels L, Sandalova E. Role of cellular immunity in cow's milk allergy: pathogenesis, tolerance induction,   and   beyond.   Mediators   Inflamm   2014;2014:249784.

26. Vordenbaumen S, Braukmann A, Altendorfer I, Bleck E, Jose J, Schneider M. Human casein alpha s1 (CSN1S1) skews in vitro differentiation of monocytes towards macrophages. BMC Immunol 2013; 14:46.

27. Hirahara  K,  Hisatsune  T,  Choi  CY,  Kaminogawa  S.Profound immunological tolerance in the antibody response against bovine alpha s1-casein induced by intradermal administration of a dominant T cell determinant. Clin Immunol Immunopathol 1995; 76(1 Pt 1):12-8.



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