Th17 and regulatory T cells contribute to thein situimmune response in skin lesions of Jorge Lobo's disease

Abstract

Jorge Lobo's disease (JLD) is a chronic granulomatous mycosis described in various Latin American countries. The main objective of the present study was to investigate the possible role of Th17 and Foxp3+ Treg cells in the pathogenesis of Jorge Lobo's disease. Human skin biopsies were submitted to an immunohistochemistry protocol to detect Foxp3, interleukin (IL)-1beta, CD25, IL-6, IL-17, and IL-23. The epidermis presented acanthosis, hyperkeratosis, and frequent presence of fungi. The dermis presented inflammatory infiltrate comprising macrophages, lymphocytes, epithelioid and multinucleated cells, and an intense number of fungi. Foxp3+ Treg cells and IL-17+ cells were visualized in lymphocytes in the inflammatory infiltrate. IL-1, IL-2R (CD25), IL-6, and IL-23 were visualized in the dermis, intermingled with fungal cells, permeating or participating of the granuloma. Following IL-17, the most prominent cytokine was IL-6. IL-23 and cells expressing CD25 were present in fewer number. The comparative analysis between IL-17 and Foxp3 demonstrated a statistically significant increased number of IL-17+ cells. Th17 cells play a role in the immune response of JLD. IL-1beta and IL-6 added to the previously described increased number of TGF-beta would stimulate such pattern of response. Th17 cells could be present as an effort to modulate the local immune response; however, high levels of a Th17 profile could overcome the role of Treg cells. The unbalance between Treg/Th17 cells seems to corroborate with the less effective immune response against the fungus.

Sporothrix brasiliensis induces a more severe disease associated with sustained Th17 and regulatory T cells responses than Sporothrix schenckii sensu stricto in mice

“…Some studies showed that Tregs increased protective immunity (Pandiyan et al, 2011, Netea et al, 2004, Schulze et al, 2014, Wiesner et al, 2016, while in other models, Tregs promoted fungal infection (Felonato et al, 2012;Whibley et al, 2014). Our results suggest that, in addition to the immunosuppressive role of Tregs in avoiding excessive inflammation, they may also favor a shift to a Th17 response, promoting the elimination of the pathogen in advanced stages of infection (Kanashiro-Galo et al, 2016;Sehrawat and Rouse, 2017). The effect of Tregs on the Th17 function in fungal infection is also controversial.…”

Analysis of Immune Response Markers in Jorge Lobo's Disease Lesions Suggests the Occurrence of Mixed T Helper Responses with the Dominance of Regulatory T Cell Activity

“…While macrophages and fibroblasts may be responsible for IL-17 expression in the lesions [ 49 , 50 , 51 ], the putative inhibitory effect that Tregs have on Th17 cells may be critical in preventing the development of comprehensive Th17 responses in the lesions. A recent study demonstrated that IL-17+ cells outnumbered FOXP3+ cells in JLD lesions [ 52 ]. This report is consistent with the findings regarding IL-17 and FOXP3 expression in the present study.…”

“…This report is consistent with the findings regarding IL-17 and FOXP3 expression in the present study. However, the previous authors concluded that high levels of Th17 cytokines could overcome the effects of Treg cells [ 52 ]. This assertion does not consider the fact that Tregs make up a very small fraction of lymphocyte subsets both, in the circulating lymphocytes pool and in inflammatory infiltrates in peripheral tissues; it is not surprising that effector cells, such as IL-17+ cells, may outnumber FOXP3+ cells [ 53 , 54 ].…”

Lacaziosis: immunohistochemical evaluation of elements of the humoral response in cutaneous lesions

“…The ineffective immune response against the agent seems to be related to a Th2-type cytokines pattern and the lesions comprise a clinical and immunological spectrum that varies from susceptible to resistant to treatment 5 . In addition, an expressive number of IL17-producing CD4+ T cells over TCD4+ Foxp3+ in lacaziosis skin lesions have been described, and it is suggested that the Th17 cytokine pattern may be present as an auxiliary mechanism for modulating the local immune response 6 . The cytotoxic function of CD8+ T cells was evidenced based on the detection of perforin and granzyme B and a role in the in situ immune response to eliminate the fungus was suggested.…”