Editing Psoriasis (section)

==Pathophysiology==
Psoriasis is characterized by an abnormally excessive and rapid growth of the [[epidermis (skin)|epidermal layer of the skin]].<ref name="Ouyang2010">{{cite journal | vauthors = Ouyang W | title = Distinct roles of IL-22 in human psoriasis and inflammatory bowel disease | journal = Cytokine & Growth Factor Reviews | volume = 21 | issue = 6 | pages = 435–41 | date = December 2010 | pmid = 21106435 | doi = 10.1016/j.cytogfr.2010.10.007 }}</ref> Abnormal production of skin cells (especially during [[wound repair]]) and an overabundance of skin cells result from the sequence of pathological events in psoriasis.<ref name="Raychaudhuri2014"/> The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease.<ref name="Nestle" /><ref name="Rendon2019" /> Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days.<ref name="Parrish2012"/> These changes are believed to stem from the premature maturation of [[keratinocyte]]s induced by an inflammatory cascade in the [[dermis]] involving [[dendritic cell]]s, [[macrophage]]s, and T cells (three subtypes of immune cells).<ref name="Palfreeman2013"/><ref name="Cedeno2011">{{cite journal | vauthors = Cedeno-Laurent F, Gómez-Flores M, Mendez N, Ancer-Rodríguez J, Bryant JL, Gaspari AA, Trujillo JR | title = New insights into HIV-1-primary skin disorders | journal = Journal of the International AIDS Society | volume = 14 | issue = 5 | pages = 5 | date = January 2011 | pmid = 21261982 | pmc = 3037296 | doi = 10.1186/1758-2652-14-5 | doi-access = free }}</ref> These immune cells move from the [[dermis]] to the epidermis and secrete inflammatory chemical signals (cytokines) such as [[IL36G|interleukin-36γ]], [[tumor necrosis factor-α]], [[Interleukin 1 family|interleukin-1β]], [[interleukin-6]], and [[interleukin-22]].<ref name=Nestle/><ref>{{cite journal | vauthors = Baliwag J, Barnes DH, Johnston A | title = Cytokines in psoriasis | journal = Cytokine | volume = 73 | issue = 2 | pages = 342–50 | date = June 2015 | pmid = 25585875 | pmc = 4437803 | doi = 10.1016/j.cyto.2014.12.014 | series = Skin Disease, Immune Response and Cytokines }}</ref> These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate.<ref name=Nestle/> One hypothesis is that psoriasis involves a defect in [[regulatory T cell]]s, and in the regulatory cytokine [[interleukin-10]].<ref name=Nestle/> The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.<ref name="Rendon2019" />

Gene mutations of proteins involved in the skin's ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.<ref name="Roberson2010">{{cite journal | vauthors = Roberson ED, Bowcock AM | title = Psoriasis genetics: breaking the barrier | journal = Trends in Genetics | volume = 26 | issue = 9 | pages = 415–23 | date = September 2010 | pmid = 20692714 | pmc = 2957827 | doi = 10.1016/j.tig.2010.06.006 }}</ref><ref name="Ramos2012">{{cite journal | vauthors = Ramos-e-Silva M, Jacques C | title = Epidermal barrier function and systemic diseases | journal = Clinics in Dermatology | volume = 30 | issue = 3 | pages = 277–9 | date = May–June 2012 | pmid = 22507041 | doi = 10.1016/j.clindermatol.2011.08.025 }}</ref>

[[Deoxyribonucleic acid]] (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis<ref name="Dombrowski2012">{{cite journal | vauthors = Dombrowski Y, Schauber J | title = Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis | journal = Experimental Dermatology | volume = 21 | issue = 5 | pages = 327–30 | date = May 2012 | pmid = 22509827 | doi = 10.1111/j.1600-0625.2012.01459.x | s2cid = 24119451 }}</ref> and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α.<ref name="Dombrowski2012"/> In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.<ref name=Nestle/>

[[Dendritic cell]]s bridge the [[innate immune system]] and [[adaptive immune system]]. They are increased in psoriatic lesions<ref name="Ouyang2010"/> and induce the proliferation of T cells and type 1 helper T cells (T<sub>h</sub>1). Targeted [[immunotherapy]], as well as [[psoralen]] and [[ultraviolet A]] ([[PUVA]]) therapy, can reduce the number of dendritic cells and favors a [[Th2 cell|T<sub>H</sub>2 cell]] cytokine secretion pattern over a T<sub>h</sub>1/T<sub>h</sub>17 cell cytokine profile.<ref name=Nestle/><ref name="Wong2013"/> Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and [[interleukin-17]].<ref name="Mudigonda2012">{{cite journal | vauthors = Mudigonda P, Mudigonda T, Feneran AN, Alamdari HS, Sandoval L, Feldman SR | title = Interleukin-23 and interleukin-17: importance in pathogenesis and therapy of psoriasis | journal = Dermatology Online Journal | volume = 18 | issue = 10 | pages = 1 | date = October 2012 | doi = 10.5070/D33N39N8XM | pmid = 23122008 }}</ref> Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22.<ref name="Ouyang2010"/><ref name="Mudigonda2012"/> Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete [[neutrophil]]-attracting cytokines.<ref name="Mudigonda2012"/>