Stromal cell Immunobiology

Lymphoid organs such as Lymph Nodes (LNs) are immune “platforms” that regulate many functions of the immune system.
Unlike most of our organs that are composed of resident and immobile cells, lymphoid organs are composed of >95% leukocytes continuously and transiently wandering amongst 5%< of resident stromal cells that constitute the “genuine” structure of these organs.

We are studying how these stromal cells regulate leukocytes "life" during their journey in these tissues.

Overview

The immune system is an army aimed to fight invading pathogens regardless the location of the infection. In order to perform their functions, endlessly mobile soldiers (lymphocytes) patrol the secondary lymphoid organs (SLOs) in search for their cognate antigen. SLOs such as spleen and lymph nodes (LNs) are dispersed throughout the body and can be compared to headquarters where lymphatic and blood derived informations converge in order to set up an appropriate immune response.

A typical lymph node is composed of 90% of wandering lymphocytes/monocytes/DCs and 10% of sessile stromal cells that form the backbone of the organ.
Among these cells, Fibroblastic Reticular Cells (FRCs) colonize the T cell zone of SLOs while Follicular Dendritic Cells (FDCs) reside in the B cell follicles. Both cell types create dense 3D networks in their respective areas.

So far, these architectural cells have received little attention but recent growing evidences suggest that they regulate the immune response in several ways:

• Using dynamic imaging, we have demonstrated that lymphocytes are crawling on these stromal cells (see movie). Of note, DCs also settle on the FRCs, fostering their constant transient interactions with motile lymphocytes.

• FDCs and FRCs control lymphocytes homeostasis by providing survival signals to B and T cells respectively. 
• FRCs create a system of pipes also called the conduit system that rapidly transports afferent lymph throughout the T cell zone, allowing DCs to get access to its content within minutes. Altogether, these observations indicate that stromal cells of SLOs organize the logistics of the immune response by providing infrastructures, conveying informations and gathering various cell types necessary to initiate an immune response. (see Fig below).

Organization and function of LN stromal cells:
Lymph drained from peripheral tissues arrives in the subcapsular sinus and enters the conduit system (1)- This 3D network of reticular fibers is produced by FRCs in the T cell zone and (i) transports the lymphatic content throughout the T cell zone while (ii) providing strength (structure) and elasticity to the LN. FRCs wrap themselves around the conduits and hence create a 3D cellular network.
Importantly, T cells migrate on the FRC network. In the mean time, FRCs secrete the T cell survival factor IL-7. In the B cell zone (#2), FDCs form a distinct cellular network that produces the B cell survival signal BAFF while supporting B cell migration. Upon an immune response, FDCs networks remodel to support the development of Germinal Centers.

Our goal is to better understand the biology of these cells. To this aim, we are undertaking an imaging based approach relying on advanced dynamic imaging techniques (2-Photon microscopy) and the generation of new mouse models.