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A Role for Asymmetric Skin Stem Cell Division in Psoriasis

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Review of “IL17A-dependent asymmetric stem cell divisions are increased in human psoriasis; a mechanism underlying benign hyperproliferation” from STEM CELLS by Stuart P. Atkinson

The inflammatory immunologic skin disease psoriasis presents with benign hyperproliferation in the stem cell/progenitor-containing layer of the skin known as the epidermis [1]. The lab of Ruby Ghadially (University of California San Francisco, USA) hypothesized that an imbalance between asymmetric (ACDs) and symmetric (SCDs) cell divisions within the epidermis might be the root cause, given the existence of a similar misbalance in cancer development.

The team’s new STEM CELLS article employed human and mouse models to study both stem cell divisional behavior and any link between the immune system and stem cell hyperproliferation [2].

When compared to normal human skin, Charruyer et al. discovered a 70-fold increase in asymmetric cell divisions (ACDs) in psoriasis, leading to the production of a stem cell and a more differentiated transit-amplifying cell, but no overall change to stem cell number. Furthermore, when the authors treated freshly isolated skin cells (keratinocytes) in vitro with factors known to associated with benign hyperproliferation (the growth factor amphiregulin and the immune factor IL-1α) or Interleukin 17A (IL17A), an important psoriasis-associated pro-inflammatory cytokine, they also observed an increased proportion of ACDs, but no change in stem cell number. 

Moving to mouse, the authors demonstrated that epidermal hyperproliferation caused by treatment with the toll-like-receptor-7 agonist imiquimod (IMQ) also led to elevated numbers of ACDs; however, IL17A neutralizing antibodies inhibited this effect, so highlighting the link between the immune system and benign hyperproliferation and vindicating potentially effective psoriasis treatment [3]. 

This intriguing new study suggests that balancing stem cell divisions is an important consideration in skin disorders such as psoriasis, and not just cancer! The authors also hope that their data will be the first step to fully understanding the links between the immune system and epidermal hyperproliferation towards forming an effective treatment option.

Keep tuned to the Stem Cells Portal to find out much more!!

References

  1. McKay IA and Leigh IM. Altered keratinocyte growth and differentiation in psoriasis. Clinics in dermatology 1995;13:105-114.
  2. Charruyer A, Fong S, Vitcov GG, et al. Brief Report: Interleukin-17A-Dependent Asymmetric Stem Cell Divisions Are Increased in Human Psoriasis: A Mechanism Underlying Benign Hyperproliferation. STEM CELLS 2017;35:2001-2007.
  3. Chiricozzi A and Krueger JG. IL-17 targeted therapies for psoriasis. Expert Opin Investig Drugs 2013;22:993-1005.