User:Immcarle1/sandbox: Difference between revisions
added key word |
No edit summary |
||
| Line 11: | Line 11: | ||
IL-17 promotes psoriasis by contributing to the inflammatory response that damages and overturns the [[Keratinocyte|keratinocyte]] cells of the epidermal layer<ref name=":0" /><ref name=":4" />. Inflammation begins with keratinocyte cells entering the final stages of their cell cycle, which activates immature [[Dendritic cell|dendritic cells]] (DC)<ref>{{Cite journal|url = |title = Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis|last = Dombrowski|first = |date = 2012|journal = Experimental dermatology|doi = |pmid = |access-date = }}</ref>. Cytokines released from DCs stimulate dying keratinocytes to secrete [[TNF-alpha]], [[IL-1]] and [[IL-6]] leading to the chemotaxis of [[T cells]], [[natural killer cells]] and [[monocytes]] to the epidermis<ref name=":2" />. These cells release IL-23 which induces the Th17 cells to produce IL-17<ref name=":5" />. |
IL-17 promotes psoriasis by contributing to the inflammatory response that damages and overturns the [[Keratinocyte|keratinocyte]] cells of the epidermal layer<ref name=":0" /><ref name=":4" />. Inflammation begins with keratinocyte cells entering the final stages of their cell cycle, which activates immature [[Dendritic cell|dendritic cells]] (DC)<ref>{{Cite journal|url = |title = Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis|last = Dombrowski|first = |date = 2012|journal = Experimental dermatology|doi = |pmid = |access-date = }}</ref>. Cytokines released from DCs stimulate dying keratinocytes to secrete [[TNF-alpha]], [[IL-1]] and [[IL-6]] leading to the chemotaxis of [[T cells]], [[natural killer cells]] and [[monocytes]] to the epidermis<ref name=":2" />. These cells release IL-23 which induces the Th17 cells to produce IL-17<ref name=":5" />. |
||
IL-17 interaction with IL-17RA receptors abundant on the keratinocyte cell surface incite the epidermal cells to increase expression of additional IL-6, [[antimicrobial peptides]], [[IL-8]], ICAM-1 and [[CCL20]] <ref>{{cite journal|last1=Martin|first1=David|title=The emerging role of IL-17 in the pathogenesis of Psoriasis: Preclinical and clinical findings|journal=The Society for Investigative Dermatology|date=2013|issue=133.1|page=17-26}}</ref><ref name=":1" /><ref name=":4" />. Increased concentration of IL-6 alters the epidermal environment by decreasing the ability of [[T-reg|T regulatory cells]] to control the behavior of Th17 cells<ref name=":5" />. Reduced regulation allows uninhibited proliferation of Th17 cells and production of IL-17 in psoriatic lesions augmenting IL-17 signaling <ref name=":7">{{cite journal|last1=Mudigonda|first1=Parvathi|title=Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis|journal=Dermatology online journal|date=2012|issue=18.10}}</ref>. Antimicrobial peptides and IL-8 attract neutrophils to the site of injury where these cells degranulate upon and phagocytose the damaged and inflamed keratinocyte cells<ref name=":0" /><ref name=":6" /><ref name=":4" />. Additionally, ICAM-1 assists in the adhesion of neutrophils to the epithelial surface and allows for entry of neutrophils from the bloodstream<ref name=":1" />. New immature DCs are also recruited by CCL20 via chemotaxis where their activation restarts and amplifies the cycle of inflammation<ref name=":6" /><ref name=":7" />. IL-17 and additional cytokines released from the influx of neutrophils, T and dendritic cells mediate effects on localized leukocytes and keratinocytes that supports the progression of psoriasis by |
IL-17 interaction with IL-17RA receptors abundant on the keratinocyte cell surface incite the epidermal cells to increase expression of additional IL-6, [[antimicrobial peptides]], [[IL-8]], ICAM-1 and [[CCL20]] <ref>{{cite journal|last1=Martin|first1=David|title=The emerging role of IL-17 in the pathogenesis of Psoriasis: Preclinical and clinical findings|journal=The Society for Investigative Dermatology|date=2013|issue=133.1|page=17-26}}</ref><ref name=":1" /><ref name=":4" />. Increased concentration of IL-6 alters the epidermal environment by decreasing the ability of [[T-reg|T regulatory cells]] to control the behavior of Th17 cells<ref name=":5" />. Reduced regulation allows uninhibited proliferation of Th17 cells and production of IL-17 in psoriatic lesions augmenting IL-17 signaling <ref name=":7">{{cite journal|last1=Mudigonda|first1=Parvathi|title=Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis|journal=Dermatology online journal|date=2012|issue=18.10}}</ref>. Antimicrobial peptides and IL-8 attract neutrophils to the site of injury where these cells degranulate upon and phagocytose the damaged and inflamed keratinocyte cells<ref name=":0" /><ref name=":6" /><ref name=":4" />. Additionally, ICAM-1 assists in the adhesion of neutrophils to the epithelial surface and allows for entry of neutrophils from the bloodstream<ref name=":1" />. New immature DCs are also recruited by CCL20 via chemotaxis where their activation restarts and amplifies the cycle of inflammation<ref name=":6" /><ref name=":7" />. IL-17 and additional cytokines released from the influx of neutrophils, T and dendritic cells mediate effects on localized leukocytes and keratinocytes that supports the progression of psoriasis by inciting chronic inflammation<ref>{{cite journal|last1=Mudigonda|first1=Parvathi|title=Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis|journal=Dermatology online journal|date=2012|issue=18.10}}</ref>. |
||
Latest revision as of 17:24, 11 February 2016
I want to describe the mechanism of IL-17 in psoriasis development.
Psoriasis
[edit]Recent work suggests the IL-23/IL-17 pathway plays a major role in the autoimmune disorder psoriasis [1][2][3]. In this condition immune cells react to inflammatory molecules released within the skin around the joints and scalp [2]. This response causes the epidermal cells to recycle more rapidly than usual, which leads to the formation of red, scaly lesions and chronic skin inflammation[3][4]. Studies conducted in mice demonstrate that removing either IL-23 or IL-17 negatively impacts the progression of psoriasis[5][6]. Mice injected with monoclonal antibodies targeting IL-17 blocked, or neutralized, down stream signaling of this cytokine and decreased epidermal hyperplasia[5]. Similarly, genetically modifying mice to not express IL-23 or IL-17 receptors significantly reduced psoriatic lesion development upon stimulation with tumor promoter 12-O-tetradecanoylphorbol-13-acetate [7].
Analysis using RT-PCR showed an enrichment of both IL-17 and its inducing cytokine IL-23 in biopsies taken from lesion versus non-lesion skin of psoriasis patients [8][2][9]. Visualization of psoriatic lesions with immunostaining showed an abundance of cells containing IL-17. The traditional Th17 cells as well as neutrophils and cytotoxic T cells containing IL-17 were localized within the psoriatic lesion[2]. Additionally, immunostaining showed a high number of dendritic cells containing the stimulatory IL-23[8]. These results indicate an excessive infiltration of proinflammatory immune cells and IL-17 are associated with the development of psoriasis.
IL-17 promotes psoriasis by contributing to the inflammatory response that damages and overturns the keratinocyte cells of the epidermal layer[2][6]. Inflammation begins with keratinocyte cells entering the final stages of their cell cycle, which activates immature dendritic cells (DC)[10]. Cytokines released from DCs stimulate dying keratinocytes to secrete TNF-alpha, IL-1 and IL-6 leading to the chemotaxis of T cells, natural killer cells and monocytes to the epidermis[4]. These cells release IL-23 which induces the Th17 cells to produce IL-17[8].
IL-17 interaction with IL-17RA receptors abundant on the keratinocyte cell surface incite the epidermal cells to increase expression of additional IL-6, antimicrobial peptides, IL-8, ICAM-1 and CCL20 [11][3][6]. Increased concentration of IL-6 alters the epidermal environment by decreasing the ability of T regulatory cells to control the behavior of Th17 cells[8]. Reduced regulation allows uninhibited proliferation of Th17 cells and production of IL-17 in psoriatic lesions augmenting IL-17 signaling [12]. Antimicrobial peptides and IL-8 attract neutrophils to the site of injury where these cells degranulate upon and phagocytose the damaged and inflamed keratinocyte cells[2][9][6]. Additionally, ICAM-1 assists in the adhesion of neutrophils to the epithelial surface and allows for entry of neutrophils from the bloodstream[3]. New immature DCs are also recruited by CCL20 via chemotaxis where their activation restarts and amplifies the cycle of inflammation[9][12]. IL-17 and additional cytokines released from the influx of neutrophils, T and dendritic cells mediate effects on localized leukocytes and keratinocytes that supports the progression of psoriasis by inciting chronic inflammation[13].
- ^ Martin, David (2013). "The emerging role of IL-17 in the pathogenesis of Psoriasis: Preclinical and clinical findings". The Society for Investigative Dermatology (133.1): 17-26.
- ^ a b c d e f Lowes, Michelle (2014). "Immunology of psoriasis". Annual review of immunology.
- ^ a b c d Hu, Yan (2011). "The IL‐17 pathway as a major therapeutic target in autoimmune diseases". Annals of the New York Academy of Sciences.
- ^ a b Baliwag, Jaymie (2015). "Cytokines in Psoriasis". Skin Disease, Immune Response and Cytokines.
- ^ a b Nakajima, Kimiko (2011). "Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model". The Journal of Immunology.
- ^ a b c d Krueger, James (2012). "IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis". Journal of Allergy and Clinical Immunology.
- ^ Martin, David (2013). "The emerging role of IL-17 in the pathogenesis of Psoriasis: Preclinical and clinical findings". The Society for Investigative Dermatology (133.1): 17-26.
- ^ a b c d Mudigonda, Parvathi (2012). "Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis". Dermatology online journal (18.10).
- ^ a b c Lin, Andrew (2011). "Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis". The Journal of Immunology.
- ^ Dombrowski (2012). "Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis". Experimental dermatology.
- ^ Martin, David (2013). "The emerging role of IL-17 in the pathogenesis of Psoriasis: Preclinical and clinical findings". The Society for Investigative Dermatology (133.1): 17-26.
- ^ a b Mudigonda, Parvathi (2012). "Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis". Dermatology online journal (18.10).
- ^ Mudigonda, Parvathi (2012). "Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis". Dermatology online journal (18.10).