0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Commentary |

Psoriasis Bench to Bedside Genetics Meets Immunology

Rajan P. Nair, PhD; Jun Ding, MS; Kristina Callis Duffin, MD; Cynthia Helms; John J. Voorhees, MD; Gerald G. Krueger, MD; Anne M. Bowcock, PhD; Goncalo R. Abeçasis, PhD; James T. Elder, MD, PhD
Arch Dermatol. 2009;145(4):462-464. doi:10.1001/archdermatol.2009.73.
Text Size: A A A
Published online

Extract

More than 25 years of accumulating evidence strongly implicates the immune system in the pathogenesis of psoriasis, including both acquired immunity (T cells) and innate host defense (macrophages, antigen-presenting cells, and keratinocytes). Psoriasis also has a strong genetic component, but the identity of the genes involved has largely remained obscure. In a study recently published in Nature Genetics,1 these 2 themes of psoriasis—genetics and immunology—come together in a coherent and clinically relevant way.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

First Page Preview

View Large
First page PDF preview

Figures

Place holder to copy figure label and caption
Figure.

Model of psoriasis integrating genetics and immunology. The majority of dermal T cells are CD4+ (purple circles). Of these, most are TH1, and approximately 5% express interleukin (IL)-17 (TH17, yellow halo). Most of the T cells in the epidermis are CD8+ (green circles), and about 5% of these express IL-17 (Tc17, yellow halo). HLA-Cw6 may be involved in the activation of CD8+ T cells by dendritic cells (DC, blue), and activated CD8+ T cells may recognize keratinocyte (KC) antigens presented in the context of HLA-Cw6. Some of these T cells are likely to be Tc17 cells. IL23A and IL12B encode the subunits of IL-23. IL23R encodes a subunit of the receptor for IL-23. IL4 and IL13 may participate in tipping the balance of CD4+ T cells toward TH2. TH1 cells stimulate the production of IL-23 by DC. In turn, IL-23 stimulates the production of IL-17 (and other cytokines such as IL-22) by TH17 cells. These cytokines stimulate KC proliferation (mitotic figures) and upregulate KC innate immune defense mechanisms, including defensin, psoriasin, and other proteins that are highly expressed in psoriasis lesions (etc). Macrophages (MΦ, orange) express tumor necrosis factor (TNF) receptors and toll-like receptors (TLRs), which signal to NF-κB in the nucleus. The proteins encoded by TNFAIP3 and TNIP1 bind to each other and block this signaling. Similar signaling pathways may also be active in other types of skin cells. IFN-γ indicates interferon gamma. Genetic regions implicated by this study are italicized and outlined in purple.

Graphic Jump Location

Tables

References

Correspondence

CME
Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.

Multimedia

Some tools below are only available to our subscribers or users with an online account.

118 Views
14 Citations
×

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
Jobs
brightcove.createExperiences();