Anatomical distribution analysis reveals lack of Langerin+ dermal dendritic cells in footpads and tail of C57BL/6 mice

Abstract

R = 0.25), whereas controls showed no correlation (R = 0.0) (see Data S1: Supporting information).Along with these results, higher antimelanocyte antibody and LPO levels in AV patients signify equal contribution of both oxidative stress and autoimmunity in disease progression. Various antioxidant enzymes can be induced by inflammatory cytokines such as TNF-a and IFN-c, which in turn increase ROS levels in vitiligo patients (18). Our recent studies also showed increased transcript levels of SOD2, SOD3 (13), TNFA (19), TNFB (20) and IFNG (21) in vitiligo patients. There are reports showing the generation of free radicals during melanogenesis which hydroxylate tyrosinase and other proteins, thereby increasing their antigenicity (22,23). Elassiuty et al., showed upregulation of heme oxygenase-1 in patients' melanocytes due to high oxidative stress (24). The build-up of ROS along with possible immune system defects allows for the inappropriate autoimmune response against melanocytes. ROS are involved in specific early events in T-cell activation and antioxidants are involved in reducing T-cell proliferation (25). We showed decreased regulatory T cells and CD4 + /CD8 + ratio in GV patients, which were positively correlated with disease onset and progression (26). High oxidative stress can lead to the breakdown of self-tolerance by releasing plethora of sequestered autoantigens and generation of neoantigens (1). ConclusionFor the first time, our study suggests that oxidative stress may be the initial triggering event to precipitate vitiligo in Gujarat population, which is then exacerbated by contribution of autoimmune factors together with oxidative stress. AcknowledgementsNCL, MD, MSM, MS, ARG, APY, VNP, FK, DJD, AP and EMS performed the experiments; NCL, MD and RB designed the research study; RB contributed essential reagents and tools; YSM, RG and ZM arranged for the blood samples; NCL, MD and RB analysed the data; NCL and MD wrote the manuscript and RB edited it. NCL and MSM thank CSIR and UGC, New Delhi, for awarding SRF and JRF, respectively. Conflict of interestsThe authors have declared no conflicting interest. Supporting InformationAdditional Supporting Information may be found in the online version of this article: Table S1. Demographic characteristics of vitiligo patients and unaffected controls.Data S1. Supporting information. Letter to the Editor repartition is unknown. Here, we found LCs in back skin, footpads and tail skin of C57BL/6, BALB/c, 129/Sv and CBA/J mice. Langerin+ dDCs were readily observed in back skin of all strains, but only in footpads and tail of BALB/c and CBA/J mice. Similarly, while LCs were equally present in all LNs and strains, Langerin+ dDCs were found in popliteal LNs (draining footpads) only in BALB/c and CBA/J mice. The sciatic LNs, which we identified as the major tail-draining lymphoid organ, were devoid of Langerin+ dDCs in all strains. Thus, functionally different DCs reside in different skin areas, with variations among mouse strains, implying a potential impact on the c...

Human skin dendritic cells can be targeted in situ by intradermal injection of antibodies against lectin receptors

“…A word of caution may be raised regarding this minute subset of skin DCs and its importance for vaccination. In the mouse, the functionally equivalent population of Langerin + dermal DCs is missing in certain locations of the body (footpad and tail skin), as recently described 49 . Similar considerations are therefore warranted for human skin as well.…”

Integrin-Alpha IIb Identifies Murine Lymph Node Lymphatic Endothelial Cells Responsive to RANKL

“…To determine whether ITGA2b is expressed by non-LN LECs, skin was processed into a cell suspension and LECs were identified as CD45 - F4/80 - gp38 + CD31 + cells. However, we saw no ITGA2b expression by FACS or qRT-PCR, neither in LECs from resting skin, after activation with imiquimod [ 25 ] or from RANK-transgenic mice overexpressing RANKL from hair follicles [ 14 , 29 ] ( panel D in S4 Fig and data not shown). Taken together, the data show that ITGA2b is restricted to subsets of LN LECs.…”

“…Adult mice were anesthetized by intraperitoneal injection of ketamine and xylazine (100 μg/g body weight and 10 μg/g body weight, respectively). Back skin or ear skin received 12.5 μg/g (0.1mg/kg body weight) of Toll-like receptor (TLR)-7 agonist imiquimod (Aldara), diluted in neutral cream (Diprobase) [ 25 ]. Back skin hair was trimmed before hair removal with cold wax (Klorane, France).…”

Langerhans cells in the sebaceous gland of the murine skin

“…We aimed at characterizing and quantifying epidermal LCs associated with the sebaceous glands visible in dermal sheets. We focused on BALB/c and C57BL/6 mice, which are frequently employed in immunological studies and exhibit distinct repartitions and phenotypes of DC subsets (3,4) (S9,S10).…”

“…In uninflamed skin, LCs lack expression of maturation markers such as CD86. The epidermal frequency of LCs is well established in different mouse strains (2–4). However, little is known about the occurrence of LCs in epidermal appendages.…”