Hair Follicles from Alopecia Areata Patients Exhibit Alterations in Immune Privilege-Associated Gene Expression in Advance of Hair Loss

Abstract

Identification of a novel population of Langerin+ dendritic cells. J Exp Med 204: 3147-56 Chen JS, Chiu HC, Hsu CJ et al. (2009) Lowenergy visible light irradiation modulates immune responses induced by epicutaneous sensitization with protein antigen. J Invest Dermatol 129:2258-64 Isacke CM (2002) Molecules in focus the hyaluronan receptor, CD44. Int J Biochem Cell Biol 34:718-21 Merad M, Ginhoux F, Collin M (2008) Origin, homeostasis and function of Langerhans cells and other langerin-expressing dendritic cells. Nat Rev Immunol 8:935-47 Mummert DI, Takashima A, Mummert ME (2004) Langerhans cells in CD44-deficient mice emigrate from the epidermis but fail to reach the lymph nodes after hapten application. J Invest Dermatol 122:846-7 Shklovskaya E, Roediger B, Fazekas de St Groth B (2008) Epidermal and dermal dendritic cells display differential activation and migratory behavior while sharing the ability to stimulate CD4+ T cell proliferation in vivo.

The role of lymphocytes in the development and treatment of alopecia areata

“…Potentially, focal infection, microtrauma, neurogenic inflammation, or endocrine dysfunction, disrupts hair follicle IP. A deficiency of some immunoregulatory factors in the hair follicle such as red/IK, an antagonist of IFNγ-induced expression of MHC class II antigens [57], may further facilitate IP breakdown. With loss of immune suppressor functions, any ectopic upregulation of MHC class I expression may be recognized by autoreactive CD8 + cytotoxic cells which are intrinsically able to perceive and be activated by very few peptide -MHC class I complexes [58].…”

Gene Expression of Indoleamine 2,3 Dioxygenase 1, Insulin-Growth Factor 1 and Red/IK Cytokine in Alopecia Areata

“…Depending on the context, IDO limits immune activator mechanisms, thus preventing a detrimental immune activity, or induces immunosuppression (Hainz et al, 2007). The study performed by Kang (Kang et al, 2010) by carrying through 265 in the anagen phase: for example, the assessment of IGF1 mARN is being linked with hair shaft elongation after successful radiation therapy (Yoon et al, 2011). Taken together, these data suggest the fact that the increased levels of IGF1 mARN in our patients reflect the tendency of the hair follicle to restore itself.…”

“…In the same study performed by Kang (Kang et al, 2010), red/IK was shown to have a lower expression in the perilesional area compared to lesional scalp specimens. The authors suggest that the relative lack of expression of red/IK might allow MHC class II antigen expression and might modulate CD3+ cell development in the hair follicle.…”

“…Paus et al (2003) underlined the fact that these molecules downregulate the expression of MHC class I molecules separately and in conjunction, while being part of the restoration mechanism of the immune privilege, a process that is initiated whenever the hair follicle suffers an immune injury. In a previous study (Kang et al, 2010) IGF1 mARN expression was several foldhigher in AA follicles compared to normal hair follicles. Our research supported these results, the fold change (FC) values of IGF1 being higher in the plate-edge area compared to the unaffected area.…”

A New Humanized Mouse Model for Alopecia Areata

“…Although the disease is not life threatening, it may lead to severe psychological disturbances, reducing the quality of life in patients of all age groups and both genders (Inui et al, 2013), which is aggravated by the lack of satisfactory therapy. While hair follicle immune privilege collapse, CD8 þ T cells, CD56þ natural killer (NK) cells, and other natural killer group 2D-positive (NKG2D þ ) cell populations as well as IFN-g secretion by these cells are all appreciated to have a key role in AA pathogenesis (Paus et al, 2005;Freyschmidt-Paul et al, 2006;Ito et al, 2008;Kang et al, 2010;Petukhova et al, 2010), the exact pathogenesis of AA remains unknown (Bertolini et al, 2012;Gilhar et al, 2012a).…”