Daniel Kaplan, MD, PhD

  • Director of the Cutaneous Biology Research Core
  • Professor of Dermatology and Immunology

Education & Training

  • Graduate School – Washington University – PhD
  • Medical School – Washington University – MD
  • Residency – Yale University – Dermatology
  • Post-Doctoral Fellowship – Yale University

Research Grants

NIH Grants:  R01, K08

Research Summary

Dr. Kaplan is a practicing Dermatologist and leads an active basic research laboratory that focuses on the mechanisms that drive skin inflammation.  As part of that, work his laboratory develops novel tools that allow him to examine the specific functions of skin-resident immune cells.  The lab-engineered mice that selectively lack Langerhans cells.  Contrary to conventional wisdom, these cells were not required for many skin immune responses but rather suppressed cutaneous immune responses leading to a major shift in the understanding of these cells.  The lab also developed a novel skin infection model using C. albicans that allow for detailed interrogation of skin immune responses.  Using this model, Langerhans cells were required for Th17 responses and dendritic cells in the dermis were required for Th1 responses.  Unexpectedly, Th17 responses provided skin protection while Th1 responses provided systemic protection thus revealing a compartmentalization of adaptive responses.  The lab also examines the innate immune response to C. albicans revealing that pain-sensing nerves in the skin directly recognize C. albicans and are required for a cascade of inflammatory events that mediate host defense. This finding is highly significant as it demonstrates that nerves in the skin are major modulators of immune responses, a very novel finding.  The lab has also found that keratinocytes determine whether immune cells can persist in the skin through a novel mechanism of transactivation of TGFb.  Currently, the lab is focused on how individual subsets of cutaneous immune cells work in concert to direct immune responses, how non-immune cells such as nerves and keratinocytes also play critical roles in directing skin immunity, and how each of these pathways can be therapeutically targeted to modify disease processes.

Representative Publications

  1. Kashem SW, Riedl MS, Yao C, Honda CN, Vulchanova L, Kaplan DH. Nociceptive Sensory Fibers Drive Interleukin-23 Production from CD301b+ Dermal Dendritic Cells and Drive Protective Cutaneous Immunity. Immunity. 2015 Sep 15;43(3):515–26.
  2. Kashem SW, Kaplan DH. Skin Immunity to Candida albicans. Trends Immunol. 2016 May 10;37(7):440–50.
  3. Kaplan DH. Ontogeny and function of murine epidermal Langerhans cells. Nat Immunol. Nature Publishing Group; 2017 Sep 19;18(10):1068–75.
  4. Bobr A, Igyarto BZ, Haley KM, Li MO, Flavell RA, Kaplan DH. Autocrine/paracrine TGF-β1 inhibits Langerhans cell migration. Proc Natl Acad Sci USA. National Acad Sciences; 2012 Jun 26;109(26):10492–7.
  5. Mohammed J, Beura LK, Bobr A, Astry B, Chicoine B, Kashem SW, et al. Stromal cells control the epithelial residence of DCs and memory T cells by regulated activation of TGF-β. Nat Immunol. Nature Research; 2016 Apr;17(4):414–21.
  6.  Kashem SW, Haniffa M, Kaplan DH. Antigen-Presenting Cells in the Skin. Annu Rev Immunol.  Annual Reviews; 2017 Apr 26;35(1):469–99.
  7. Kaplan DH. Ontogeny and function of murine epidermal Langerhans cells. Nat Immunol. Nature Publishing Group; 2017 Sep 19;18(10):1068–75.
  8. Igyarto BZ, Haley K, Ortner D, Bobr A, Gerami-Nejad M, Edelson BT, et al. Skin-resident murine dendritic cell subsets promote distinct and opposing antigen-specific T helper cell responses. Immunity. 2011 Aug 26;35(2):260–72.
  9. Haley K, Igyarto BZ, Ortner D, Bobr A, Kashem S, Schenten D, et al. Langerhans cells require MyD88-dependent signals for Candida albicans response but not for contact hypersensitivity or migration. J Immunol. 2012 May 1;188(9):4334–9.
  10. Kashem SW, Igyarto BZ, Gerami-Nejad M, Kumamoto Y, Mohammed J, Jarrett E, et al. Candida albicans Morphology and Dendritic Cell Subsets Determine T Helper Cell Differentiation. Immunity. 2015 Feb 17;42(2):356–66.
  11. Yao C, Kaplan DH. Langerhans Cells Transfer Targeted Antigen to Dermal Dendritic Cells and Acquire Major Histocompatibility Complex II In Vivo. J Invest Dermatol. 2018 Feb 21.
  12. Yao C, Zurawski SM, Jarrett ES, Chicoine B, Crabtree J, Peterson EJ, et al. Skin dendritic cells induce follicular helper T cells and protective humoral immune responses. J Allergy Clin Immunol. 2015 Nov;136(5):1387–97.e1–7.