title: T regulatory cells and plasmocytoid dentritic cells in hansen disease: a new insight into pathogenesis?
abstract: Leprosy is characterized by spectrum of histologically different granulomatous skin lesions that reflects the patient's immune response to Mycobacterium leprae. Presence, frequency, and distribution of both CD4+ CD25+ FoxP3+ T regulatory cells (T-regs) and CD123+ plasmacytoid dendritic cells in leprosy have never been investigated. We performed a retrospective immunohistochemical study on 20 cases of leprosy [tuberculoid tuberculoid (TT): 1 patient; borderline tuberculoid (BT): 3 patients; borderline lepromatous (BL): 5 patients; lepromatous lepromatous (LL): 5 patients; borderline borderline in reversal reaction (BB-RR): 1 patient; BT-RR: 2 patients; and erythema nodosum leprosum (ENL): 3 patients]. FoxP3-positive cells were present in 95% of the cases with an average density of 2.9% of the infiltrate. Their distribution was not related to granulomatous structures or special locations. There was no statistical difference of FoxP3 expression between TT, BT, BL, and LL, whereas a statistical significant increment (P = 0.042) was observed in patients affected by reversal leprosy reactions (BT-RR and BB-RR) compared with patients affected by ENL and patients with nonreactional disease forms (BL, LL, BT, TT). CD123 expression was not observed in any of the biopsy specimens evaluated; with the exception of 2 cases of ENL, in which a focal positivity for CD123 was observed. Our results show that plasmacytoid dendritic cells are not involved in the immune response against M. leprae while T-regs are present in leprosy skin lesions. These data raise the question if T-regs have a pathogenetic role in HD as previously demonstrated in Leishmania major and Mycobacterium tuberculosis.
authors.affiliation: From the *Department of Dermatology, Medical University of Graz, Graz, Austria; †Unit of Social Dermatology, National Reference Center for Hansen's Disease, Azienda Ospedaliera Universitaria "San Martino" di Genova and Department of Health Sciences, University of Genoa, Genoa, Italy; ‡Department of Pathology & Núcleo de Doenças Infecciosas, Universidade Federal do Espírito Santo, Vitória, ES, Brazil; §Department of Dermatology, Institute of Tropical Medicine of Amazonas; ¶Foundation Alfredo Da Matta, Manaus, AM, Brazil; ∥Department of Dermatology; and **Department of Oncology, Clinical Sperimentation and Biostatistic, Galliera Hospital, Genoa, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Massone
authors.forename: Enrico
authors.initials: E
authors.lastname: Nunzi
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Ribeiro-Rodrigues
authors.forename: Carolina
authors.initials: C
authors.lastname: Talhari
authors.forename: Sinésio
authors.initials: S
authors.lastname: Talhari
authors.forename: Antonio Pedro Mendes
authors.initials: APM
authors.lastname: Schettini
authors.forename: José Napoleão Tavares
authors.initials: JNT
authors.lastname: Parente
authors.forename: Alexandra Mg
authors.initials: AM
authors.lastname: Brunasso
authors.forename: Matteo
authors.initials: M
authors.lastname: Puntoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Clapasson
authors.forename: Salvatore
authors.initials: S
authors.lastname: Noto
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerroni
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D053650:Interleukin-3 Receptor alpha Subunit / Q000378:metabolism; D007918:Leprosy / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
chemical_list: D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit