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Papers of the Week

Papers: 22 Feb 2020 - 28 Feb 2020

Animal Studies, Human Studies

2020 Feb 26

Sci Transl Med



Blood natural killer cell deficiency reveals an immunotherapy strategy for atopic dermatitis.


Mack MR, Brestoff JR, Berrien-Elliott MM, Trier AM, Yang T-LB, McCullen M, Collins PL, Niu H, Bodet ND, Wagner JA, Park E, Xu AZ, Wang F, Chibnall R, Council LM, Heffington C, Kreisel F, Margolis DJ, Sheinbein D, Lovato P, et al.
Sci Transl Med. 2020 Feb 26; 12(532).
PMID: 32102931.


Atopic dermatitis (AD) is a widespread, chronic skin disease associated with aberrant allergic inflammation. Current treatments involve either broad or targeted immunosuppression strategies. However, enhancing the immune system to control disease remains untested. We demonstrate that patients with AD harbor a blood natural killer (NK) cell deficiency that both has diagnostic value and improves with therapy. Multidimensional protein and RNA profiling revealed subset-level changes associated with enhanced NK cell death. Murine NK cell deficiency was associated with enhanced type 2 inflammation in the skin, suggesting that NK cells play a critical immunoregulatory role in this context. On the basis of these findings, we used an NK cell-boosting interleukin-15 (IL-15) superagonist and observed marked improvement in AD-like disease in mice. These findings reveal a previously unrecognized application of IL-15 superagonism, currently in development for cancer immunotherapy, as an immunotherapeutic strategy for AD.