scholarly journals Tsc1 expression by dendritic cells is required to preserve T-cell homeostasis and response

2017 ◽  
Vol 8 (1) ◽  
pp. e2553-e2553 ◽  
Author(s):  
Yuechen Luo ◽  
Wenwen Li ◽  
Gang Yu ◽  
Juan Yu ◽  
Ling Han ◽  
...  
2013 ◽  
Vol 210 (10) ◽  
pp. 2011-2024 ◽  
Author(s):  
Nathan E. Welty ◽  
Christopher Staley ◽  
Nico Ghilardi ◽  
Michael J. Sadowsky ◽  
Botond Z. Igyártó ◽  
...  

Dendritic cells (DCs) in the intestinal lamina propria (LP) are composed of two CD103+ subsets that differ in CD11b expression. We report here that Langerin is expressed by human LP DCs and that transgenic human langerin drives expression in CD103+CD11b+ LP DCs in mice. This subset was ablated in huLangerin-DTA mice, resulting in reduced LP Th17 cells without affecting Th1 or T reg cells. Notably, cognate DC–T cell interactions were not required for Th17 development, as this response was intact in huLangerin-Cre I-Aβfl/fl mice. In contrast, responses to intestinal infection or flagellin administration were unaffected by the absence of CD103+CD11b+ DCs. huLangerin-DTA x BatF3−/− mice lacked both CD103+ LP DC subsets, resulting in defective gut homing and fewer LP T reg cells. Despite these defects in LP DCs and resident T cells, we did not observe alterations of intestinal microbial communities. Thus, CD103+ LP DC subsets control T cell homeostasis through both nonredundant and overlapping mechanisms.


Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 518-518
Author(s):  
Tadafumi Iino ◽  
Hiromi Iwasaki ◽  
Kentaro Kohno ◽  
Shin-ichi Mizuno ◽  
Yojiro Arinobu ◽  
...  

Abstract Abstract 518 PU.1, a hematopoietic transcription factor, is indispensable for development of conventional dendritic cells (cDCs) from hematopoietic stem cells. However, the function of PU.1 in mature cDC remains unclear. To test the possible role of PU.1 in mature cDCs, we developed mice lacking PU.1 selectively in mature cDCs (DC-PU.1D/D mice) by crossing a PU.1flox mouse line with a transgenic Itgax (CD11c)-Cre strain. In these mice, cDCs were dramatically reduced in spleen, thymus, lymph node, and skin, down to <40%, <25%, <10% and <5% of DCs in control mice respectively, whereas bone marrow cDCs and common dendritic cells progenitors (CDPs) were not affected. Surprisingly, T cell numbers were significantly decreased in DC-PU.1D/D mice, whereas thymic T cell development was normal, suggesting that maintenance of mature T cell pool might be impaired, presumably by dysfunction of PU.1D/D cDCs. In fact, PU.1D/D cDCs failed to efficiently induce ovalbumin-specific T cell response and to produce inflammatory cytokines in response to Toll like receptor (TLR) stimulation both in vitro and in vivo. The intravenous transfer of spleen PU.1D/D cDCs failed to repopulate the spleen of recipient mice, suggesting their poor survival in vivo. Furthermore, the expression of critical molecules for inflammatory responses was downregulated in PU.1D/D cDCs as compared to normal cDCs. These molecules included Myd88 and NFkB that are downstream molecules of TLR signaling, CD86 that is required for T cell stimulation, and CCR7 that is required for cDC migration. These results clearly show that PU.1 is required for development of the functional cDC pool, and the cDC pool plays a critical role in T cell homeostasis. Disclosures: No relevant conflicts of interest to declare.


2011 ◽  
Vol 121 (7) ◽  
pp. 2898-2910 ◽  
Author(s):  
Christian Weber ◽  
Svenja Meiler ◽  
Yvonne Döring ◽  
Miriam Koch ◽  
Maik Drechsler ◽  
...  

Immunity ◽  
2011 ◽  
Vol 35 (6) ◽  
pp. 945-957 ◽  
Author(s):  
Meike Wendland ◽  
Stefanie Willenzon ◽  
Jessica Kocks ◽  
Ana Clara Davalos-Misslitz ◽  
Swantje I. Hammerschmidt ◽  
...  

Blood ◽  
2008 ◽  
Vol 112 (12) ◽  
pp. 4546-4554 ◽  
Author(s):  
Spencer W. Stonier ◽  
Lisa J. Ma ◽  
Eliseo F. Castillo ◽  
Kimberly S. Schluns

AbstractInterleukin-15 (IL-15) is crucial for the development of naive and memory CD8 T cells and is delivered through a mechanism called transpresentation. Previous studies showed that memory CD8 T cells require IL-15 transpresentation by an as yet unknown cell of hematopoietic origin. We hypothesized that dendritic cells (DCs) transpresent IL-15 to CD8 T cells, and we examined this by developing a transgenic model that limits IL-15 transpresentation to DCs. In this study, IL-15 transpresentation by DCs had little effect on restoring naive CD8 T cells but contributed to the development of memory-phenotype CD8 T cells. The generation of virus-specific, memory CD8 T cells was partially supported by IL-15Rα+ DCs through the preferential enhancement of a subset of KLRG-1+CD27− CD8 T cells. In contrast, these DCs were largely sufficient in driving normal homeostatic proliferation of established memory CD8 T cells, suggesting that memory CD8 T cells grow more dependent on IL-15 transpresentation by DCs. Overall, our study clearly supports a role for DCs in memory CD8 T-cell homeostasis but also provides evidence that other hematopoietic cells are involved in this function. The identification of DCs fulfilling this role will enable future studies to better focus on mechanisms regulating T-cell homeostasis.


Immunity ◽  
2016 ◽  
Vol 44 (4) ◽  
pp. 860-874 ◽  
Author(s):  
Katarzyna M. Luda ◽  
Thorsten Joeris ◽  
Emma K. Persson ◽  
Aymeric Rivollier ◽  
Mimoza Demiri ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document