A Non‐Coding Oligonucleotide Recruits Cutaneous CD11b+ Cells that Inhibit Thelper Responses and Promote Tregs

Author:

Kamal Kahkashan1ORCID,Richardsdotter‐Andersson Elina2ORCID,Dondalska Aleksandra1ORCID,Wahren‐Herlenius Marie2ORCID,Spetz Anna‐Lena1ORCID

Affiliation:

1. Department of Molecular Biosciences The Wenner‐Gren Institute Stockholm University Svante Arrhenius väg 20C Stockholm SE‐106 91 Sweden

2. Department of Medicine Karolinska University Hospital Karolinska Institutet Visionsgatan 18, L8 Solna SE‐171 76 Sweden

Abstract

AbstractSkin‐resident antigen‐presenting cells (APC) play an important role in maintaining peripheral tolerance via immune checkpoint proteins and induction of T regulatory cells (Tregs). However, there is a lack of knowledge on how to expand or recruit immunoregulatory cutaneous cells without causing inflammation. Here, it is shown that administration of a non‐coding single‐stranded oligonucleotide (ssON) leads to CCR2‐dependent accumulation of CD45+CD11b+Ly6C+ cells in the skin that express substantial levels of PD‐L1 and ILT3. Transcriptomic analyses of skin biopsies reveal the upregulation of key immunosuppressive genes after ssON administration. Functionally, the cutaneous CD11b+ cells inhibit Th1/2/9 responses and promote the induction of CD4+FoxP3+ T‐cells. In addition, ssON treatment of imiquimod‐induced inflammation results in significantly reduced Th17 responses. It is also shown that induction of IL‐10 production in the presence of cutaneous CD11b+ cells isolated after ssON administrations is partly PD‐L1 dependent. Altogether, an immunomodulatory ssON is identified that can be used therapeutically to recruit cutaneous CD11b+ cells with the capacity to dampen Th cells.

Funder

Vetenskapsrådet

Stockholms Universitet

Publisher

Wiley

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