International Journal of Clinical Dermatology & Research (IJCDR)    IJCDR-2332-2977-04-001e

The Guardians of the Skin Immune System


Tapia FJ*, Rodríguez OL

Universidad Central de Venezuela and Ministerio de Salud, Venezuela.

*Corresponding Author

Felix J. Tapia,
Associate Professor, Universidad Central de Venezuela,
Venezuela.
Email: felix.tapia@gmail.com

Received: April 16, 2016; Published: April 20, 2016

Citation: Tapia FJ, Rodríguez OL, (2016) The Guardians of the Skin Immune System .Int J Clin Dermatol Res. 4(1e), 1. DOI : dx.doi.org/10.19070/2332-2977-160004e

Copyright: Tapia FJ© 2016. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the original author and source are credited.


It has been well established that the epithelia are major components of the immune system. Together with secondary lymphoid organs (ig. lymph nodes, Payer´s patch, etc.), they comprise the activation sites of the Skin and Mucosal Immune Systems, also known as Peripheral or Tegumentary Immune System. Therefore, the epidermis is an essential place for immune modulation.

Based on a series of articles by Ralf Paus and collaborators from the University of Hamburg in Germany, in relation to hair follicle as a zone of immune privilege, we now know that a series of molecules produced by keratinocytes may play a key role in controlling skin homeostasis. These molecules are pleiotropic bioactive peptides, such as alpha-melanocyte-stimulating hormone (α-MSH), insulinlike growth factor 1 (IGF-1), indoleamine 2,3-dioxygenase (IDO), interleukin-10 (IL-10), IL-6, transforming growth factor-beta1 (TGF-β1) and neuroimmune regulatory proteins (e.g. CD200, CD47).

For instance, TGF-β1 induces stimulatory or inhibitory effects in human T cells, which is dependent on the T cell differentiation status and the stimulation conditions. Thus, TGF-β1 has distinct roles in T cell development, homeostasis, tolerance and differentiation.

The events that occur in wound-healing and the role of TGF-β1 may place these ideas into context. Recent evidences suggest that the release of enzymes generates by trauma, such as tryptases, promote epithelial cell division and produce essential guardians factors such as IL-6, TGF-β1, platelet-activating endothelial factor (PAF), α-MSH and IGF-I, which are crucial in enabling the recruitment of cells with active dermotropism.

Shortly after the initial injury coagulation occurs. There, platelets secrete platelet-derived growth factor (PDGF), TGF-β, and platelet factor IV, that initiate the wound-healing cascade by attracting fibroblasts, endothelial cells and macrophages into the wound. Platelets also secrete vasoactive neuropeptides, such as serotonin and histamine, which increase local microvascular permeability, allowing more inflammatory cells to infiltrate the wound.

In early inflammatory phase, the neutrophil is the predominant cell type, capable of preventing infection and removing debris by releasing proteinases and other enzymes into the wound. During late inflammatory response, macrophages, which are drawn to the wound by epithelial TGF-β, PDGF and various complement components, produce more TGF-β, PDGF, IGF- 1 and basic fibroblast growth factor (bFGF). These cytokines regulate the production and organization of the extracellular matrix by fibroblasts, and the proliferation of smooth muscle cells and endothelial cells necessary for angiogenesis. The recruited fibroblasts begin to synthesise collagen starting in the remodelling phase of wound repair.

It is important to keep an eye on these epithelial guardians of the immune homeostasis, more that looking into inflammatory responses that most probably are an epiphenomenon.



References

  1. Paus R, Nickoloff BJ, Ito T (2005) A ‘hairy’ privilege. Trends Immunol 26(1): 32-40.
  2. Paus R, Ito N, Takigawaw M, Ito T (2003) The Hair Follicle and Immune Privilege. J Investig Dermatol Symp Proc 8(2): 188-194.
  3. Beanes SR, Dang C, Soo C, Ting K (2003) Skin repair and scar formation: the central role of TGF-beta. Expert Rev Mol Med 5(8): 1-22.
  4. Paus R, Theoharides TC, Arck PC (2006) Neuroimmunoendocrine circuitry of the 'brain-skin connection'. Trends Immunol 27(1): 32-39.
  5. Paus R, Bertolini M (2013) The role of hair follicle immune privilege collapse inalopecia areata: status and perspectives. J Investig Dermatol Symp Proc 16(1): S25-27.
  6. Kinori M, Kloepper JE, Paus R ( 2011) Can the hair follicle become a model for studying selected aspects of human ocular immune privilege? Invest Ophthalmol Vis Sci 52(7): 4447-4458.

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