Kirsner, Robert S.

Tzu, Julia

Vega, Janelle

Elsevier - Publisher Connector 

journal club
2740 Journal of Investigative Dermatology (2009), Volume 129 © 2009 The Society for Investigative Dermatology
For the article: http://dx.doi.org/10.1038/jid.2009.176
QUESTIONS
1. How is antigen thought to be presented?
2. How and why were the murine models used in the study developed?
3. How were the relative contributions of the different cell types to the graft-versus-host disease model determined?
4. What were the results of the study?
5. What were limitations of the study?
6. What were the conclusions of the study?
To better understand T-cell immunity, investigators at the National Institutes of Health used 
a variety of murine models to study the relative contributions of the antigen-presenting 
cells (APCs) of the skin. Specifically, Kim and co-workers in the laboratory of Steve Katz 
attempted to characterize the ability of Langerhans cells (LCs) and dermal dendritic cells 
(dDCs) to present antigen (Ag) in a modified mouse model of graft-versus-host disease 
(GVHD) (2009, this issue). After eliminating LCs via targeted diphtheria toxin in genetically 
susceptible mice and altering the antigen-presenting capability of dermal dendritic cells 
by bone marrow transplantation with β2-microglobulin-deficient cells, the invest igators 
observed an unexpected phenomenon. When both LCs and dDCs were impaired, a 
GVHD reaction still occurred, presumably through keratinocyte-mediated antigen presentation. Keratinocytes were also found 
to be able to prime naive skin-reactive T cells.
These observations are part of an evolving understanding of skin immunity. Although it has been appreciated for 
some time that LCs and dDCs take up antigen in the periphery and migrate to regional lymph nodes, their ability to 
induce and maintain tolerance is a more recent observation, and much remains uncertain. For example, in studies 
of LCs in contact hypersensitivity reactions (CHS), three disparate outcomes have been observed: (i) no effect, (ii) 
attenuation, or (iii) enhancement of CHS responses (Bennett et al., 2005; Kaplan et al., 2005; Kissenpfennig et al., 2005). 
At the very least, the experiments in which LCs either had no effect or caused attenuation of CHS suggest that dDCs 
are likely to be important in mediating CHS. Additionally, the absence of LCs, which were long thought to be critical in 
skin graft rejection, was recently reported to enhance graft rejection in mice mismatched for minor histocompatibility 
antigens (Obhrai et al., 2008).
In the context of our changing understanding of the skin immune system, Kim and colleagues sought to add clarity 
using a novel methodology. Through the following questions, we will examine this paper and skin immunity in greater 
detail. For discussion and brief answers, please refer to the supplementary information linked to the online version of 
the paper at http://www.nature.com/jid.
references
Bennett CL, van Rijn E, Jung S, Inaba K, Steinman RM, Kapsenberg ML et al. (2005) Inducible ablation of mouse Langerhans cells diminishes but fails to 
abrogate contact hypersensitivity. J Cell Biol 169:569–76
Kaplan DH, Jenison MC, Saeland S, Shlomchik WD, Shlomchik MJ (2005) Epidermal Langerhans cell–deficient mice develop enhanced contact 
hypersensitivity. Immunity 23:611–20
Kim bS, Miyagawa F, cho Y-H, bennett cl, clausen bE, Katz SI (2009) Keratinocytes function as accessory cells for presentation of endogenous antigen 
expressed in the epidermis. J Invest Dermatol 129:2805–17
Kissenpfennig A, Henri S, Dubois B, Laplace-Builhe C, Perrin P, Romani N et al. (2005) Dynamics and function of Langerhans cells in vivo: dermal 
dendritic cells colonize lymph node areas distinct from slower migrating Langerhans cells. Immunity 22:643–54
Obhrai JS, Oberbarnscheidt M, Zhang N, Mueller DL, Shlomchik WD, Lakkis FG et al. (2008) Langerhans cells are not required for efficient skin graft 
rejection. J Invest Dermatol 128:1950–5
re-examining cutaneous Immunity
Janelle Vega1, Julia Tzu1 and Robert S. Kirsner1
Journal of Investigative Dermatology (2009) 129, 2740. doi:10.1038/jid.2009.351
1Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, Florida, USA


Re-Examining Cutaneous Immunity 

Vega, Janelle

Tzu, Julia

Kirsner, Robert S

University of Miami: Scholarship Miami

Journal of Investigative Dermatology

Re-Examining Cutaneous Immunity

Janelle  Vega

Julia Tzu

Robert S. Kirsner

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Re-Examining Cutaneous Immunity

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Elsevier - Publisher Connector

Elsevier - Publisher Connector

University of Miami: Scholarship Miami

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