Brief communication: Long-term absence of Langerhans cells alters the gene expression profile of keratinocytes and dendritic epidermal T cells

Abstract

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells' biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active role in maintaining tissue homeostasis, which should be taken in consideration at data interpretation.

The mRNA-LNP platform's lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

“…Total RNA was analyzed for quantity and quality using the RNA 6000 Pico Kit (Agilent). Sequencing, data analyses and visualization were performed as we and others previously described in details (Kanehisa, 2000;Liberzon et al, 2011;Love et al, 2014;Su et al, 2020;Subramanian et al, 2005).…”

The mRNA-LNP platform’s lipid nanoparticle component used in preclinical vaccine studies is highly inflammatory

“…Of note, since PEG is a compound frequently used in cosmetics and toothpaste, many individuals could have anti-PEG antibodies. We have discussed other possible mechanisms in our recent opinion article (Igyártó et al, 2020). Briefly, while mRNA mainly transfects cells near the injection site it could hypothetically reach any cell in the body (Maugeri et al, 2019;Pardi et al, 2015).…”

“…Total RNA was analyzed for quantity and quality using the RNA 6000 Pico Kit (Agilent). Sequencing, data analyses and visualization were performed as we and others previously described (Kanehisa and Goto, 2000; Liberzon et al, 2011; Love et al, 2014; Su et al, 2020; Subramanian et al, 2005).…”

Meeting Report of the 16th International Langerhans Cell Workshop: Recent Developments in Langerhans Cell and Skin Dendritic Cell Biology and their Therapeutic Application

“…These observations support Florent Ginhoux's notion that LCs, which have a common embryonic origin with macrophages, contribute to maintain skin homeostasis (see above), in addition to their well-known antigen-presenting DC function. Moreover, the novel data put forward by the Kaplan laboratory extend initial reports that long-term absence of LCs impairs epidermal barrier function (Lee et al, 2019) and alters the gene expression profile of keratinocytes and dendritic epidermal T cells (Su et al, 2020). On the other hand, why acute depletion of LCs in essentially the same mice also leads to enhanced CHS responses (Bobr et al, 2010), in contrast to other inducible LC-depletion models (Clausen and Stoitzner, 2015), remains elusive.…”