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Leitner, J.

Publications and source records attributed to Leitner, J..

2 recordsLinked to original sources
bioRxiv2022

Interoperability of RTN1A in dendrite dynamics and immune functions in human Langerhans cells

Skin is an active immune organ where professional antigen-presenting cells such as epidermal Langerhans cells (LCs) link innate and adaptive immune responses. While Reticulon 1A (RTN1A) was recently identified in LCs and dendritic cells in cutaneous and lymphoid tissues of humans and mice, its function is still unclear. Here, we studied the involvement of this protein in cytoskeletal remodeling and immune responses towards pathogens by stimulation of Toll-like receptors (TLRs) in resident LCs (rLCs) and emigrated LCs (eLCs) in human epidermis ex vivo and in a transgenic THP-1 RTN1A+ cell line. Hampering RTN1A functionality through an inhibitory antibody induced significant dendrite retraction of rLCs and inhibited their emigration. Similarly, expression of RTN1A in THP-1 cells significantly altered their morphology, enhanced aggregation potential and inhibited the Ca2+ flux. Differentiated THP-1 RTN1A+ macrophages exhibited long cell protrusions and a larger cell body size in comparison to wild type cells. Further, stimulation of epidermal sheets with bacterial lipoproteins (TLR1/2 and TLR2) and single-stranded RNA (TLR7) resulted in the formation of substantial clusters of rLCs and a significant decrease of RTN1A expression in eLCs. Together, our data indicate involvement of RTN1A in dendrite dynamics and structural plasticity of primary LCs. Moreover, we discovered a relation between activation of TLRs, clustering of LCs and downregulation of RTN1A within the epidermis, thus indicating an important role of RTN1A in LC residency and maintaining tissue homeostasis. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=127 SRC="FIGDIR/small/487626v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@8011c8org.highwire.dtl.DTLVardef@f784borg.highwire.dtl.DTLVardef@1a28a1corg.highwire.dtl.DTLVardef@195b0f_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIBlocking of RTN1A induces dendrite retraction of resident LCs (rLCs) in epidermal explants. C_LIO_LIDespite a roundish morphology rLCs exhibit reduced migration capacity. C_LIO_LIRTN1A has an inhibitory effect on the calcium flux. C_LIO_LIToll-like receptor-activated rLCs form vast clusters and significantly diminish RTN1A expression after emigration. C_LIO_LIRTN1A plays a central role in LC residency and maintaining tissue homeostasis. C_LI

cell biology↗
bioRxiv2018

Neural Mechanisms Associated with Semantic and Basic Self-Oriented Memory Processes Interact to Modulate Self-Esteem.

Individuals constantly encounter feedback from others and process this feedback in various ways to maintain positive situational state self-esteem (SSE) in relation to semantic-based or trait self-esteem (TSE). Individuals may utilize a data-driven, or episodic-based process that encodes positive, but not negative, self-relevant information automatically, or employ a semantic-driven process that manipulates encoded negative feedback post-hoc. Its unclear, however, how these processes work either alone or in concert while individuals receive positive and negative feedback to modulate feedback encoding and subsequent SSE. Utilizing neural regions associated with semantic self-oriented and basic encoding processes (mPFC and PCC respectively), and time-frequency and Granger causality analyses to assess mPFC and PCC interactions, this study examined how encoding of positive and negative self-relevant feedback modulated individuals post-task SSE in relation to their TSE while continuous EEG was recorded. Among those with higher levels of TSE, the encoding of positive or negative feedback was not associated with SSE. Rather, higher SSE was associated with mPFC activity to all feedback and higher TSE. The relationship between TSE and SSE was moderated by mPFC-PCC communication such that increases in mPFC-PCC communication led to SSE levels that were consistent with TSE levels. Furthermore, Granger causality analyses indicated that individuals exhibited higher SSE to the extent mPFC influenced PCC in response to positive and negative feedback. Findings highlight the dynamic interplay between semantic self-oriented and basic encoding processes that modulate SSE in relation to TSE, to maintain more positive global selfperceptions in the moment and over time.

neuroscience↗