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Chemokine Signaling in Allergic Contact Dermatitis: Toward Targeted Therapies

Smith, Jeffrey S., BS*; Rajagopal, Sudarshan, MD, PhD*†; Atwater, Amber Reck, MD

doi: 10.1097/DER.0000000000000391

Allergic contact dermatitis (ACD) is a common skin disease that results in significant cost and morbidity. Despite its high prevalence, therapeutic options are limited. Allergic contact dermatitis is regulated primarily by T cells within the adaptive immune system, but also by natural killer and innate lymphoid cells within the innate immune system. The chemokine receptor system, consisting of chemokine peptides and chemokine G protein–coupled receptors, is a critical regulator of inflammatory processes such as ACD. Specific chemokine signaling pathways are selectively up-regulated in ACD, most prominently CXCR3 and its endogenous chemokines CXCL9, CXCL10, and CXCL11. Recent research demonstrates that these 3 chemokines are not redundant and indeed activate distinct intracellular signaling profiles such as those activated by heterotrimeric G proteins and β-arrestin adapter proteins. Such differential signaling provides an attractive therapeutic target for novel therapies for ACD and other inflammatory diseases.

From the Departments of *Biochemistry,

Medicine, and

Dermatology, Duke University, Durham, NC.

Address reprint requests to Amber Reck Atwater, MD, Department of Dermatology, Duke University Medical Center, 5324 McFarland Rd #210, Durham NC 27707. E-mail:

Supported by T32GM7171 (to J.S.S.), 1R01GM122798-01A1 (to S.R.), K08HL114643-01A1 (to S.R.), Burroughs Wellcome Career Award for Medical Scientists (to S.R.), and the Duke Pinnell Center for Investigative Dermatology (to J.S.S., A.R.A., and S.R.).

The authors have no conflicts of interest to declare.

© 2018 American Contact Dermatitis Society
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