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1.
Semin Immunopathol ; 43(4): 519-533, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34230995

RESUMO

The liver is an important immunological site that can promote immune tolerance or activation. Natural killer (NK) cells are a major immune subset within the liver, and therefore understanding their role in liver homeostasis and inflammation is crucial. Due to their cytotoxic function, NK cells are important in the immune response against hepatotropic viral infections but are also involved in the inflammatory processes of autoimmune liver diseases and fatty liver disease. Whether NK cells primarily promote pro-inflammatory or tolerogenic responses is not known for many liver diseases. Understanding the involvement of NK cells in liver inflammation will be crucial in effective treatment and future immunotherapeutic targeting of NK cells in these disease settings. Here, we explore the role that NK cells play in inflammation of the liver in the context of viral infection, autoimmunity and fatty liver disease.


Assuntos
Doenças Autoimunes , Hepatopatias , Humanos , Inflamação , Células Matadoras Naturais , Fígado
2.
Mucosal Immunol ; 14(3): 605-614, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33772147

RESUMO

Gastrointestinal viral infections are a major global cause of disease and mortality in infants. Cytotoxic CD8+ T cells are critical to achieve viral control. However, studies investigating the development of CD8+ T cell immunity in human tissues early in life are lacking. Here, we investigated the maturation of the CD8+ T cell compartment in human fetal, infant and adult intestinal tissues. CD8+ T cells exhibiting a memory phenotype were already detected in fetal intestines and increased after birth. Infant intestines preferentially harbored effector CCR7-CD45RA-CD127-KLRG1+/- CD8+ T cells compared to tissue-resident memory CD69+CD103+CD8+ T cells detected in adults. Functional cytotoxic capacity, including cytokine and granzyme B production of infant intestinal effector CD8+ T cells was, however, markedly reduced compared to adult intestinal CD8+ T cells. This was in line with the high expression of the inhibitory molecule PD-1 by infant intestinal effector CD8+ T cells. Taken together, we demonstrate that intestinal CD8+ T cell responses are induced early in human development, however exhibit a reduced functionality. The impaired CD8+ T cell functionality early in life contributes to tolerance during foreign antigen exposure after birth, however functions as an immune correlate for the increased susceptibility to gastrointestinal viral infections in infancy.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Intestinos/imunologia , Células T de Memória/imunologia , Viroses/imunologia , Citotoxicidade Imunológica , Suscetibilidade a Doenças , Feminino , Feto , Regulação da Expressão Gênica no Desenvolvimento , Humanos , Tolerância Imunológica , Lactente , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo
3.
J Drugs Dermatol ; 2(2): 147-52, 2003 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-12852366

RESUMO

The purpose of this open-label study was to determine the adverse event rate of topical 4HA/tretinoin when used twice daily for up to 24 weeks with concomitant sunscreen in the treatment of solar lentigines and related hyperpigmented lesions. There were two treatment areas: bilateral dorsal forearms, including the back of the hands; and the face, including the forehead and cheek areas. Each treatment area had a target lesion at least 5 mm in diameter and was moderately darker than the surrounding skin. A nine-point bipolar scale was used for evaluation of Target Lesion Pigmentation (0 = extremely lighter than pigment of the surrounding skin, 4 = equal with pigment of surrounding skin, 8 = extremely darker than pigment of surrounding skin). The other solar lentigines present in the treatment areas also had to have an overall pigmentation grade of at least Grade 6. Twice daily applications to individual lesions in each treatment area were made for up to 24 weeks followed by a 4-week follow-up phase. Sunscreen applications (sunscreen with sun protection factor (SPF) 25 or greater) were made every morning and reapplied after six hours if additional sun exposure was expected. Clinical evaluations were performed at weeks 0, 4, 8, 16, 24 and 28. The clinical signs of Target Lesion Pigmentation and Overall Lesion Pigmentation were evaluated at each visit. A total of 96 subjects were enrolled at four study centers; 77 (80%) subjects completed the study. Treatment-related adverse events (AEs) for 4HA/tretinoin included erythema, burning/stinging/tingling, desquamation, pruritus, skin irritation, halo hypopigmentation and hypopigmentation. Five (5%) subjects discontinued from the study due to adverse events considered to be related to study medication. When used with sunscreen of SPF 25 or greater, 4HA/tretinoin was safe and well tolerated and did not produce any unexpected or unusual adverse events.


Assuntos
Anisóis/uso terapêutico , Hiperpigmentação/tratamento farmacológico , Protetores Solares/uso terapêutico , Tretinoína/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Hiperpigmentação/patologia , Masculino , Pessoa de Meia-Idade
4.
J Am Acad Dermatol ; 32(1): 67-72, 1995 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-7822519

RESUMO

BACKGROUND: Plaque psoriasis of mild to moderate severity is routinely treated with topical steroids and coal tar along with emollients. A safe and convenient new treatment modality would be of value to most patients with psoriasis. OBJECTIVE: Our purpose was to evaluate the safety and efficacy of a new vitamin D3 analogue, calcipotriene, for the treatment of plaque psoriasis. METHODS: Twice-daily dosing of calcipotriene was compared with its vehicle, for up to 8 weeks, in a double-blind study of 277 patients at 10 study centers in the United States. Two hundred forty-seven patients completed the trial. The clinical characteristics of plaque elevation, erythema, scaling, and overall disease severity were evaluated at baseline and after 1, 2, 4, 6, and 8 weeks of treatment. A Physician's Global Assessment of improvement or worsening of the disease was performed after 1, 2, 4, 6, and 8 weeks of treatment. Blood and urine samples, for routine clinical laboratory tests, were collected at baseline and after 1, 2, 4, and 8 weeks of treatment. RESULTS: As early as the week 1 evaluation, patients treated with calcipotriene ointment 0.005% had significantly lower mean scores (p = 0.043) than the vehicle-treated patients for the disease characteristics of plaque elevation, erythema, and scaling. This trend continued through week 8 of treatment when 70% of the calcipotriene-treated patients showed 75% or more improvement compared with only 19% of vehicle-treated patients. Only minor treatment-related adverse events were observed. There were no abnormal laboratory results judged related to treatment and the rare instances of elevated serum calcium values were equally distributed between active and vehicle treatments. CONCLUSION: This study provides evidence that calcipotriene is a safe, effective, and promising new agent for the treatment of moderately severe plaque psoriasis.


Assuntos
Calcitriol/análogos & derivados , Fármacos Dermatológicos/uso terapêutico , Psoríase/tratamento farmacológico , Administração Cutânea , Adulto , Idoso , Idoso de 80 Anos ou mais , Calcitriol/uso terapêutico , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pomadas , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
6.
J Dermatol Surg Oncol ; 18(4): 316-20, 1992 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-1560156

RESUMO

Sunscreens reduce the deleterious effects of ultraviolet radiation (UVR) by absorbing, reflecting, or scattering photons. Ultraviolet radiation includes UVB, which is primarily responsible for sunburn and skin cancers, as well as UVA, which has been implicated in photoaging. Topical photoprotective agents include physical and chemical sunscreens. Physical sunscreens are important in individuals who are unusually sensitive to UVA and visible light such as those with photosensitizing diseases. Chemical sunscreens are more cosmetically appealing and can selectively absorb UVB and/or UVA. The increased awareness of the importance of sun protection has encouraged the regular use of sunscreens. This article will review physical and chemical sunscreens. The properties and vehicle design of various sunscreen formulations are also discussed.


Assuntos
Protetores Solares , Administração Tópica , Humanos , Protetores Solares/administração & dosagem
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