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Vitiligo and dendritic cells

Jusleen Ahluwalia, Lilia M Correa-Selm, Babar K Rao
Melanocytes, the cells responsible for skin pigmentation, are present in other parts of the body, such as the ocular, auditory, nervous, and cardiac systems. Within these systems, their roles serve a different purpose than their classical counterparts in skin as pigment cells. Such roles include cell turnover in retinal pigment epithelium, maintenance of balance and prevention of environmental damage in the auditory neuroepithelium, role-playing as dendritic cells within the leptomeninges, and prevention of oxidative damage in adipose tissue...
2017: Skinmed
C Jacquemin, J Rambert, S Guillet, D Thiolat, N Boukhedouni, M-S Doutre, A-S Darrigade, K Ezzedine, P Blanco, A Taieb, K Boniface, J Seneschal
BACKGROUND: Plasmacytoid dendritic cells (pDCs) are a subset of dendritic cells specialized in the production of type I interferon (IFN-α/β) and involved in various cutaneous inflammatory and autoimmune disorders, such as cutaneous lupus erythematosus (CLE) and vitiligo. Heat shock proteins (HSPs) are molecular chaperones essential for maintaining cellular functions, but they can act as a danger signal during inflammation. OBJECTIVES: To decipher the role of HSP70 in the production of IFN-α by pDCs in CLE and vitiligo...
November 2017: British Journal of Dermatology
Qi-Lin Li, Yan-Hua Wu, Mu Niu, Xiao-Juan Lu, Yong-Hua Huang, Dan-Hua He
BACKGROUND: Oxidative damage may lead to the dysfunction of melanocytes (MCs) and is one of the causative mechanisms involved in the pathogenesis of vitiligo. OBJECTIVES: This study was designed to investigate the protective effects of the vitamin D3 analog tacalcitol on oxidative damage induced by hydrogen peroxide (H2 O2 ) in human epidermal MCs. METHODS: Human epidermal MCs were cultured and identified by l-DOPA staining and HMB-45 immunohistochemical staining...
February 2017: International Journal of Dermatology
Kyle A Wilson, Stephen R Goding, Harold R Neely, Kristina M Harris, Paul Andrew Antony
Five-year survival rates for patients diagnosed with metastatic melanoma are less than 5%. Adoptive cell transfer (ACT) has achieved an objective response of 50% by Response Evaluation Criteria in Solid Tumors (RECIST) in this patient population. For ACT to be maximally effective, the host must first be lymphodepleted. It is hypothesized that lymphodepletion may remove regulatory elements and cytokine sinks, or increase the activation and availability of antigen presenting cells (APCs). We use an in vivo model to study the ACT of tumor-associated antigen (TAA)-specific CD4(+) T cells (TRP-1 cells)...
August 2015: Oncoimmunology
Heng Xie, Fubo Zhou, Ling Liu, Guannan Zhu, Qiang Li, Chunying Li, Tianwen Gao
Vitiligo is a common depigmentation disorder characterized by a loss of functional melanocytes and melanin from epidermis, in which the autoantigens and subsequent autoimmunity caused by oxidative stress play significant roles according to hypotheses. Various factors lead to reactive oxygen species (ROS) overproduction in the melanocytes of vitiligo: the exogenous and endogenous stimuli that cause ROS production, low levels of enzymatic and non-enzymatic antioxidants, disturbed antioxidant pathways and polymorphisms of ROS-associated genes...
January 2016: Journal of Dermatological Science
Qianqian Wang, Xiuxiu Wang, Yan Le, Min Jiang, Jiaqiang Wu, Li Tao, Yuli Kang, Leihong Xiang
BACKGROUND: Impaired dendrite outgrowth of melanocytes is one of the reasons triggering vitiligo. RNASET2 was identified as one of the risk genes for vitiligo in a GWAS study conducted in the Chinese Han population. However, the role of Rnaset2 in the outgrowth of melanocytes is rarely studied. OBJECTIVE: This study is to investigate the effects of Rnaset2 in regulating the outgrowth of melanocytes and its interacting proteins. METHODS: Stress conditions (UV irradiation, hydrogen peroxide, and lipopolysaccharides) were applied to primary human epidermal melanocytes (HEMs) and epidermal keratinocytes (HEKs)...
October 2015: Journal of Dermatological Science
Evan J Lipson, William H Sharfman, Shuming Chen, Tracee L McMiller, Theresa S Pritchard, January T Salas, Susan Sartorius-Mergenthaler, Irwin Freed, Sowmya Ravi, Hao Wang, Brandon Luber, Janice Davis Sproul, Janis M Taube, Drew M Pardoll, Suzanne L Topalian
BACKGROUND: Limited adjuvant treatment options exist for patients with high-risk surgically resected melanoma. This first-in-human study investigated the safety, tolerability and immunologic correlates of Melanoma GVAX, a lethally irradiated granulocyte-macrophage colony stimulating factor (GM-CSF)-secreting allogeneic whole-cell melanoma vaccine, administered in the adjuvant setting. METHODS: Patients with stage IIB-IV melanoma were enrolled following complete surgical resection...
July 5, 2015: Journal of Translational Medicine
Carmela Rozera, Giancarlo Antonini Cappellini, Giuseppina D'Agostino, Laura Santodonato, Luciano Castiello, Francesca Urbani, Iole Macchia, Eleonora Aricò, Ida Casorelli, Paola Sestili, Enrica Montefiore, Domenica Monque, Davide Carlei, Mariarosaria Napolitano, Paola Rizza, Federica Moschella, Carla Buccione, Roberto Belli, Enrico Proietti, Antonio Pavan, Paolo Marchetti, Filippo Belardelli, Imerio Capone
BACKGROUND: Advanced melanoma patients have an extremely poor long term prognosis and are in strong need of new therapies. The recently developed targeted therapies have resulted in a marked antitumor effect, but most responses are partial and some degree of toxicity remain the major concerns. Dendritic cells play a key role in the activation of the immune system and have been typically used as ex vivo antigen-loaded cell drugs for cancer immunotherapy. Another approach consists in intratumoral injection of unloaded DCs that can exploit the uptake of a wider array of tumor-specific and individual unique antigens...
2015: Journal of Translational Medicine
Vedrana Bulat, Mirna Situm, Dora Madiraca, Kristina Majcen, Antea Dzapo, Josip Jezovita
Vitiligo is an acquired, chronic, multifactorial disorder which involves complex interactions between genetic risk factors and environmental triggers. It is characterized by scattered circumscribed depigmented macules and patches anywhere on the skin that result from loss of functional melanocytes. According to our statistical data, 1.6% of the general population in Croatia suffers from vitiligo, but varies based on region. It affects all age groups equally, with female patients being more affected (53.95%) than male patients, and no difference in severity of vitiligo...
December 2014: Collegium Antropologicum
Akram Beheshti, Hodda Ghadami, Ameneh Barikani, Fatemeh Haj Manouchehri
Vitiligo Vulgaris is a pigment disorder as the lack of skin pigmentation which its most prevalent cause is autoimmune. Vitamin D has various effects on the natural and acquired immune of the body because of its effectiveness on the T cells and B cells, macrophages and dendritic cells.The object of this study was assessment of the Vitamin D in patients with vitiligo vulgaris in dermatologic clinics in Qazvin in 2012. The 100 patients with Vitiligo were studied through a cross-sectional study. The required data were collected by the questionnaire (age, gender, job, family background, consumption of the dairies and vitamin D supplements), examination (type of skin) and para clinical test (measurement of the serum 25-hydroxyvitamin D level)...
2014: Acta Medica Iranica
Clarissa Luiza Dalla Bernardina Carvalho, Luciena Cegatto Martins Ortigosa
The tumor necrosis factor alpha is a cytokine related to immune and inflammatory processes by acting on different parts of the body. It is secreted by several cell types including macrophages, lymphocytes, monocytes, neutrophils, dendritic cells, among others. Infliximab is a chimeric monoclonal antibody that specifically binds to soluble and transmembrane tumor necrosis factor alpha form blocking its action. In rheumatoid arthritis it is used because the cytokines that cause inflammation in this disease are regulated by tumor necrosis factor alpha and IL-1...
January 2014: Anais Brasileiros de Dermatologia
Antoine Bertolotti, Katia Boniface, Beatrice Vergier, Djavad Mossalayi, Alain Taieb, Khaled Ezzedine, Julien Seneschal
Immune-mediated responses are consistently observed in progressing vitiligo at the edge of depigmenting patches. Besides the role of the adaptive immune system, the profile of the innate immune response is now at the center of the stage. We report that plasmacytoid dendritic cells (pDC), which are the major interferon (IFN)-alpha-producing cells, are part of the infiltrate of progressive vitiligo with local production of MxA (a protein induced by IFNα). MxA was associated with expression of the type I IFN-inducible ligand CXCL9 and correlated with the recruitment of CXCR3(+) immune cells...
May 2014: Pigment Cell & Melanoma Research
S S Awad
BACKGROUND: Phototherapy is a well-known method to treat vitiligo and is able to repopulate the skin with new melanocytes. Examination of the pathological changes in vitiligo after ultraviolet therapy revealed the presence of unusual cells. AIM OF STUDY: This study intended to investigate and confirm the repopulation of epidermis with new spindle cells, possibly as precursors for melanocytes after UV therapy. METHODS: Retrospective study was carried out on paraffin sections of biopsies obtained from 30 vitiligo patients treated successfully with ultraviolet therapy...
December 2014: Journal of the European Academy of Dermatology and Venereology: JEADV
Daguang Wang, Xihui Xu, Huijun Ma, Xuezhuang Yue, Chengrang Li, Wenyuan Zhu
The melanocytes in vitiligo repigmentation are derived predominantly from melanocyte precursors (MPs) present in the outer root sheath (ORS) of hair follicles. The methods currently used for culturing MPs are unstable, and the cultured cells have the capacity to produce melanin. These factors are problematic when conducting in vitro studies to investigate the mechanism of repigmentation. Although 1,25-dihydroxyvitamin D3 (VID) has been demonstrated to be highly effective in the treatment of vitiligo in the clinic, its precise mode of action has yet to be elucidated...
October 2013: Experimental and Therapeutic Medicine
Naoki Oiso, Atsushi Tanemura, Yorihisa Kotobuki, Masatomo Kimura, Ichiro Katayama, Akira Kawada
Vitiligo is an acquired disorder in which depigmented macules result from mostly autoimmune loss of melanocytes. The initiating process in vitiligo has still been uncertain. Here, we report the case of a 19-year-old man with undetermined/unclassified vitiligo with a new periphery-spreading vitiligo lesion on the right dorsal hand after rigorous sun exposure. Histopathological evaluation showed noticeable infiltration of CD68(+) macrophages, moderate infiltration of CD3(+) T cells, little infiltration of CD8(+) T cells and CD11c(+) myeloid dendritic cells, HMB45/CD11c double-positive cells, and Melan-A/MART1(+) deposits in the dermis...
November 2013: Journal of Dermatology
Arnaud Pommier, Alexandra Audemard, Aurélie Durand, Renée Lengagne, Arnaud Delpoux, Bruno Martin, Laetitia Douguet, Armelle Le Campion, Masashi Kato, Marie-Françoise Avril, Cédric Auffray, Bruno Lucas, Armelle Prévost-Blondel
The present study evaluates the impact of immune cell populations on metastatic development in a model of spontaneous melanoma [mice expressing the human RET oncogene under the control of the metallothionein promoter (MT/ret mice)]. In this model, cancer cells disseminate early but remain dormant for several weeks. Then, MT/ret mice develop cutaneous metastases and, finally, distant metastases. A total of 35% of MT/ret mice develop a vitiligo, a skin depigmentation attributable to the lysis of normal melanocytes, associated with a delay in tumor progression...
August 6, 2013: Proceedings of the National Academy of Sciences of the United States of America
Jeffrey A Mosenson, Jonathan M Eby, Claudia Hernandez, I Caroline Le Poole
Inducible heat-shock protein 70 (HSP70i) is a protein regulated by stress that protects cells from undergoing apoptosis. Such proteins are marvellously well conserved throughout evolution, which has placed them in the spotlight for helping to understand the intriguing relationship between infection and immunity. In the presence of stress proteins, dendritic cells (DCs) will sense this alarm signal and respond by recruiting immune cells of different plumage to fit the occasion. In times of stress, melanocytes will secrete antigen-bound HSP70i to act as an alarm signal in activating DCs that comes equipped with an address of origin to drive the autoimmune response in vitiligo...
September 2013: Experimental Dermatology
S Sanchez-Sosa, M Aguirre-Lombardo, G Jimenez-Brito, A Ruiz-Argüelles
The pathogenesis of vitiligo is still controversial. The purpose of this study was to gain insight into the nature of lymphoid cells infiltrating depigmented areas of skin in vitiligo. Immunochemical procedures were carried out in biopsies from 20 patients with active lesions to search for cells expressing CD1a, CD2, CD3, CD4, CD5, CD8, CD20, CD25, CD30, CD56, CD68 and CD79a. Results indicate that early lesions are infiltrated mainly by dendritic cells, whereas older lesions display significantly lower proportions of these cells and increased percentages of mature T cells...
August 2013: Clinical and Experimental Immunology
Jeffrey A Mosenson, Andrew Zloza, John D Nieland, Elizabeth Garrett-Mayer, Jonathan M Eby, Erica J Huelsmann, Previn Kumar, Cecele J Denman, Andrew T Lacek, Frederick J Kohlhapp, Ahmad Alamiri, Tasha Hughes, Steven D Bines, Howard L Kaufman, Andreas Overbeck, Shikhar Mehrotra, Claudia Hernandez, Michael I Nishimura, Jose A Guevara-Patino, I Caroline Le Poole
Vitiligo is an autoimmune disease characterized by destruction of melanocytes, leaving 0.5% of the population with progressive depigmentation. Current treatments offer limited efficacy. We report that modified inducible heat shock protein 70 (HSP70i) prevents T cell-mediated depigmentation. HSP70i is the molecular link between stress and the resultant immune response. We previously showed that HSP70i induces an inflammatory dendritic cell (DC) phenotype and is necessary for depigmentation in vitiligo mouse models...
February 27, 2013: Science Translational Medicine
Jeffrey A Mosenson, Andrew Zloza, Jared Klarquist, Allison J Barfuss, Jose A Guevara-Patino, I Caroline Le Poole
HSP70i and other stress proteins have been used in anti-tumor vaccines. This begs the question whether HSP70i plays a unique role in immune activation. We vaccinated inducible HSP70i (Hsp70-1) knockout mice and wild-type animals with optimized TRP-1, a highly immunogenic melanosomal target molecule. We were unable to induce robust and lasting depigmentation in the Hsp70-1 knockout mice, and in vivo cytolytic assays revealed a lack of cytotoxic T-lymphocyte activity. Absence of T-cell infiltration to the skin and maintenance of hair follicle melanocytes were observed...
January 2012: Pigment Cell & Melanoma Research
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