Vol 12, Núm 2

Inmunología y homeóstasis: conceptos actuales y perspectivas.

Bracamonte-Baran William

 

Texto completo [PDF]

Resumen (ES)

Immunology is a field that has grown enormously in terms of its intrinsic understanding and clinical practice. It has been also remarkable the discovery of its influence in other systems of the organism, of which it seemed to be isolated. It is key to point out that interaction of the immune system with others does not occur only during an external insult, but also during physiological homeostasis. It has been discovered that the immune system, beyond its antimicrobial function, plays a critical role in the regulation of many biological functions; including mucosal integrity, hemodynamics and even metabolism, amongst others. The independence of systems and sub-systems has to be revised, since an integrative understanding is required. Important modifications have to be implemented in our educational systems in order to achieve an appropriated teaching method of the ubiquitous concepts of immunology. In this review/opinion article, the modern non-classical concepts of immunology will be discussed, with special emphasis on: infiltration and residence, microenvironment, interaction with non-leukocyte cells (stroma/parenchyma), non-canonical functions of the immune system and leukocytes regulators. This review also contains opinions and hypotheses of which as author I am entirely responsible. Finally, more than a specific revision, this article aims to draw the holistic view of the immune system in physiological homeostasis, considering the most modern concepts and evidence.

Keywords: immunolgy, homeostasis, regulation.

 

Resumen (ES)

La inmunología es un campo que no solo ha tenido un crecimiento enorme en cuanto a su comprensión intrínseca y práctica clínica, sino además en el descubrimiento de su influencia en otros sistemas del organismo de los cuales parecía estar aislada. Es de importancia vital el hecho de que dicha interacción del sistema inmunológico con otros no ocurre solo durante una noxa externa, sino también durante la homeostasis fisiológica. Se ha descubierto que el sistema inmunológico, mas allá de su función de defensa, funge un rol esencial en la regulación de múltiples funciones biológicas, incluyendo la integridad de las mucosas, la hemodinámica e incluso el metabolismo, entre muchos otros. La independencia de los sistemas y sub-sistemas ha de ser revisada, pues una comprensión integradora es requerida. Modificaciones importantes han de ser implementadas en nuestros sistemas educativos a fin de lograr una enseñanza adecuada de los conceptos ubicuos de la inmunología. En esta revisión/artículo de opinión serán discutidos los conceptos modernos no-clásicos de la inmunología, con énfasis especial en: infiltración y residencia, microentorno (microenvironment), interacción con células no leucocitarias (estroma/parénquima), funciones no canónicas del sistema inmunológico y leucocitos reguladores. Esta revisión contiene además opiniones e hipótesis de las cuales como autor me hago enteramente responsable. Más que una revisión fáctica puntual, este artículo pretende dibujar la visión holística del sistema inmunológico en la homeostasis fisiológica basado en los conceptos y evidencias más modernas.

Palabras clave: Inmunología; homeostasis; regulación.

Licencia de Creative Commons

Referencias bibliográficas

  1. Ginhoux F, Guilliams M. TissueResident Macrophage Ontogeny and Homeostasis. Immunity, 2016. 44(3): p. 439-449.
  2. Mold JE, Anderson CC. A discussion of immune tolerance and the layered immune system hypothesis. Chimerism, 2013. 4(3): p. 62-70.
  3. Ginhoux F. Jung SD. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol, 2014. 14(6): p. 392-404.
  4. Shi C, Pamer EG. Monocyte recruitment during infection and infl Nat Rev Immunol, 2011. 11(11): p. 762-74.
  5. Theriault P, ElAli A, Rivest S, The dynamics of monocytes and microglia in Alzheimer’s disease. Alzheimers Res Ther, 2015. 7(1): p. 41.
  6. Eberl G, et al., Innate lymphoid cells. Innate lymphoid cells: a new paradigm in immunology. Science, 2015. 348(6237): p. aaa6566.
  7. Diefenbach A, Colonna M, Koyasu S, Development, differentiation, and diversity of innate lymphoid cells. Immunity, 2014. 41(3): p. 354-65.
  8. Gasteiger, G., et al., Tissue residency of innate lymphoid cells in lymphoid and nonlymphoid organs. Science, 2015. 350(6263): p. 981-5.
  9. Gajewski, T.F., H. Schreiber, and Y.X. Fu, Innate and adaptive immune cells in the tumor microenvironment. Nat Immunol, 2013. 14(10): p. 1014-22.
  10. Rahat, M.A. and J. Shakya, Parallel Aspects of the Microenvironment in Cancer and Autoimmune Disease. Mediators Inflamm, 2016. 2016: p. 4375120.
  11. Ohkura, N., Y. Kitagawa, and S. Sakaguchi, Development and maintenance of regulatory T cells. Immunity, 2013. 38(3): p. 414-23.
  12. Burkett, P.R., G. Meyer zu Horste, and V.K. Kuchroo, Pouring fuel on the fre: Th17 cells, the environment, and autoimmunity. J Clin Invest, 2015. 125(6): p. 2211-9.
  13. Chen, X. and J.J. Oppenheim, Th17 cells and Tregs: unlikely allies. J Leukoc Biol, 2014. 95(5): p. 723-731.
  14. Tsai, H.C., et al., IL-17A and Th17 cells in lung inflammation: an update on the role of Th17 cell differentiation and IL-17R signalling in host defense against infection. Clin Dev Immunol, 2013. 2013: p. 267971.
  15. Sehrawat, S. and B.T. Rouse, Interplay of Regulatory T Cell and Th17 Cells during Infectious Diseases in Humans and Animals. Front Immunol, 2017. 8: p. 341.
  16. Zhang, Q., N. Yu, and C. Lee, Mysteries of TGF-beta Paradox in Benign and Malignant Cells. Front Oncol, 2014. 4: p. 94.
  17. Nishino, M., et al., Monitoring immune-checkpoint blockade: response evaluation and biomarker development. Nat Rev Clin Oncol, 2017. 14(11): p. 655-668.
  18. Korman, A.J., K.S. Peggs, and J.P. Allison, Checkpoint blockade in cancer immunotherapy. Adv Immunol, 2006. 90: p. 297-339.
  19. Garcia-Diaz, A., et al., Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell Rep, 2017. 19(6): p. 1189-1201.
  20. Martin, N.T. and M.U. Martin, Interleukin 33 is a guardian of barriers and a local alarmin. Nat Immunol, 2016. 17(2): p. 122-31.
  21. Kakkar, R. and R.T. Lee, The IL-33/ ST2 pathway: therapeutic target and novel biomarker. Nat Rev Drug Discov, 2008. 7(10): p. 827-40.
  22. Palomares, O., et al., Mechanisms of immune regulation in allergic diseases: the role of regulatory T and B cells. Immunol Rev, 2017. 278(1): p. 219-236.
  23. Saluja, R., et al., The role of IL- 33 and mast cells in allergy and infl Clin Transl Allergy, 2015. 5: p. 33.
  24. Anzai, A., et al., The infarcted myocardium solicits GM-CSF for the detrimental oversupply of inflammatory leukocytes. J Exp Med, 2017. 214(11): p. 3293-3310.
  25. Guglani, L. and S.A. Khader, Th17 cytokines in mucosal immunity and infl Curr Opin HIV AIDS, 2010. 5(2): p. 120-7.
  26. Kempski, J., et al., TH17 Cell and Epithelial Cell Crosstalk during Inflammatory Bowel Disease and carcinogenesis. Front Immunol, 2017. 8: p. 1373.
  27. Bordon, Y., Immunometabolism. ILC2s skew the fat. Nat Rev Immunol, 2015. 15(2): p. 67.
  28. O’Sullivan, T.E. and J.C. Sun, Innate Lymphoid Cell Immunometabolism. J Mol Biol, 2017. 429(23): p. 3577-3586.
  29. Dart, M.L., et al., Interleukin-17-dependent autoimmunity to collagen type V in atherosclerosis. Circ Res, 2010. 107(9): p. 1106-16.
  30. Park, A.C., et al., Mucosal Administration of Collagen V Ameliorates the Atherosclerotic
    Plaque Burden by Inducing Interleukin 35-dependent Tolerance. J Biol Chem, 2016. 291(7): p. 3359-70.
  31. Zeng, Y., et al., Roles of mechanical force and CXCR1/CXCR2 in shearstress-induced endothelial cell migration. Eur Biophys J, 2012. 41(1): p. 13-25.
  32. Bracamonte-Baran, W., Dinámica de fluidos computacional aplicada al estudio del flujo sanguíneo en el cayado aórtico humano y sus principales ramas. Ingeniería, Investigación y Tecnología, 2016. 17(1): p. 45-60.
  33. Vigano, S., et al., Positive and negative regulation of cellular immune responses in physiologic conditions and diseases. Clin Dev Immunol, 2012. 2012: p. 485781.
  34. Klein, L., et al., Positive and negative selection of the T cell repertoire: what thymocytes see (and don’t see). Nat Rev Immunol, 2014. 14(6): p. 377-91.
  35. Danke, N.A., et al., Autoreactive T cells in healthy individuals. J Immunol, 2004. 172(10): p. 5967-72.
  36. Choi, J., et al., IL-35 and Autoimmunity: a Comprehensive Perspective. Clin Rev Allergy Immunol, 2015. 49(3): p. 327-32.
  37. Tomita, Y., et al., Kinetics of Alloantigen-Specifc Regulatory CD4 T Cell Development and Tissue Distribution After Donor-Specifc Transfusion and Costimulatory Blockade. Transplant Direct, 2016. 2(5): p. e73.
  38. Kieback, E., et al., Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity. Immunity, 2016. 44(5): p. 1114-26.
  39. Ray, A. and B.N. Dittel, Mechanisms of Regulatory B cell Function in Autoimmune and Inflammatory Diseases beyond IL-10. J Clin Med, 2017. 6(1).
  40. Passos, L.S., et al., Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection. BMC Infect Dis, 2017. 17(1): p. 253.
  41. Liu, J. and X. Cao, Regulatory dendritic cells in autoimmunity: A comprehensive review. J Autoimmun, 2015. 63: p. 1-12.
  42. Bracamonte-Baran, W., et al., Modifcation of host dendritic cells by microchimerism-derived extracellular vesicles generates split tolerance. Proc Natl Acad Sci U S A, 2017. 114(5): p. 1099-1104.
  43. Morelli, A.E., W. BracamonteBaran, and W.J. Burlingham, Donor-derived exosomes: the trick behind the semidirect pathway of allorecognition. Curr Opin Organ Transplant, 2017. 22(1): p. 46-54.
  44. Bracamonte-Baran W. Burlingham WJ. Non inherited maternal antigens, pregnancy, and allotolerance. Biomed J, 2015. 38(1): p.39-51.