T regulatory cells and plasmocytoid dentritic cells in hansen disease: a new insight into pathogenesis?
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.
Massone
Cesare
C
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.
Nunzi
Enrico
E
Ribeiro-Rodrigues
Rodrigo
R
Talhari
Carolina
C
Talhari
Sinésio
S
Schettini
Antonio Pedro Mendes
APM
Parente
José Napoleão Tavares
JNT
Brunasso
Alexandra Mg
AM
Puntoni
Matteo
M
Clapasson
Andrea
A
Noto
Salvatore
S
Cerroni
Lorenzo
L
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
D015415:Biomarkers; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C115022:IL3RA protein, human; D053650:Interleukin-3 Receptor alpha Subunit