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De La Cruz Diaz JS, Hirai T, Anh-Thu Nguyen B, et al. TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation. JID Innov. 2021;1(3):100028doi: 10.1016/j.xjidi.2021.100028.
De La Cruz Diaz, J. S., Hirai, T., Anh-Thu Nguyen, B., Zenke, Y., Yang, Y., Li, H., Nishimura, S., & Kaplan, D. H. (2021). TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation. JID innovations, 1(3), 100028. https://doi.org/10.1016/j.xjidi.2021.100028
De La Cruz Diaz, Jacinto S, et al. "TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation." JID innovations vol. 1,3 (2021): 100028. doi: https://doi.org/10.1016/j.xjidi.2021.100028
De La Cruz Diaz JS, Hirai T, Anh-Thu Nguyen B, Zenke Y, Yang Y, Li H, Nishimura S, Kaplan DH. TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation. JID Innov. 2021 May 24;1(3):100028. doi: 10.1016/j.xjidi.2021.100028. eCollection 2021 Sep. PMID: 34909727; PMCID: PMC8659779.
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JID Innov. 2021 May 24;1(3):100028. doi: 10.1016/j.xjidi.2021.100028. eCollection 2021 Sep.

TNF-α and IL-1β Do Not Induce Langerhans Cell Migration by Inhibiting TGFβ Activation.

JID innovations

Jacinto S De La Cruz Diaz, Toshiro Hirai, Breanna Anh-Thu Nguyen, Yukari Zenke, Yi Yang, Haiyue Li, Stephen Nishimura, Daniel H Kaplan

Affiliations

  1. Department of Dermatology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  2. Department of Immunology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
  3. Department of Dermatology, St. Luke's International Hospital, Tokyo, Japan.
  4. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China.
  5. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
  6. The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
  7. School of Medicine, Tsinghua University, Beijing, China.
  8. Department of Pathology, University of California San Francisco, San Francisco, California, USA.

PMID: 34909727 PMCID: PMC8659779 DOI: 10.1016/j.xjidi.2021.100028

Abstract

In the skin, Langerhans cells (LCs) require autocrine latent TGFβ that is transactivated by the integrins ανβ6 and ανβ8 expressed by keratinocytes (KCs) for long-term epidermal retention. Selective expression of a ligand-independent, constitutively active form of TGFβR1 inhibits LC migration during homeostasis and in response to UVB exposure. In this study, we found that LC migration in response to inflammatory stimuli was also inhibited by ligand-independent TGFβR1 signaling. Contrary to UVB stimulation, which reduced KC expression of ανβ6, in vitro and in vivo exposure to TNF-α or IL-1β increased ανβ6 transcript and protein expression by KCs. This resulted in increased KC-mediated transactivation of latent TGFβ. Expression of ανβ8 was largely unchanged. These findings show that ligand-independent TGFβR1 signaling in LCs can overcome inflammatory migration stimuli, but reduced KC-mediated transactivation of latent TGFβ by KCs may only drive LC migration during homeostasis and in response to UV stimulation.

© 2021 The Authors.

Keywords: DMBA, 7,12-dimethylbenz[a]anthracene; EpCAM, epithelial cell adhesion molecule; IFE, interfollicular; IM, infundibulum/isthmus; KC, keratinocyte; LAP, latency associated peptide; LC, Langerhans cell; LN, lymph node; MHC, major histocompatibility complex; pKC, primary keratinocyte

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