The fibroblastic T cell niche in lymphoid tissues

Lymph node fibroblastic reticular cells steer immune responses

“…Nonhematopoietic-derived FRCs in mammalian LNs crucially regulate innate and adaptive immune responses. By producing growth factors, chemokines, or cytokines or presenting antigens, FRCs support LN architecture and vasculature, generating extracellular matrix (ECM) components and choreographing the survival, activation, proliferation, differentiation, and crosstalk of immune cells [ 1 , 2 ]. Recent progress in single-cell genetic analyses and high-resolution imaging and the availability of various reporter mice have revealed the extensive heterogeneity of FRCs.…”

“…TRCs can directly and indirectly regulate T cell positioning, survival, and differentiation. For indirect effects, FRCs can form different niches that facilitate T–DC interactions [ 1 , 15 , 28 ]. For direct regulation, mouse and human FRCs can limit T effector functions through nitric oxide (NO) or constitutive cyclooxygenase (COX) enzymes [ 1 , 8 ].…”

“…For indirect effects, FRCs can form different niches that facilitate T–DC interactions [ 1 , 15 , 28 ]. For direct regulation, mouse and human FRCs can limit T effector functions through nitric oxide (NO) or constitutive cyclooxygenase (COX) enzymes [ 1 , 8 ]. As revealed by co-culture of human FRCs with CD4 + or CD8 + T cells, FRCs can also mediate T cell anergy by expressing indoleamine-2,3-dioxygenase, the adenosine 2A receptor, prostaglandin E 2 , and the transforming growth factor beta receptor (TGFβR), which act to constrain the proliferation of both naïve and preactivated T cells, skewing their differentiation away from a central memory T cell phenotype [ 29 ].…”

Differentiation and activation of fibroblastic reticular cells

“…FRCs crucially contribute to an efficient adaptive immune response by secretion of stimulatory factors and cytokines including BAFF, IL-6, and IL-33 70,72,123 and express activating molecules such as major histocompatibility complex (MHC) molecules that most likely influence antiviral CD8 + T cell priming. 72,124 Concomitantly, FRCs are involved in modulating adaptive immune responses via the expression of peripheral tissue antigens, 3 inhibitory molecules such as programmed death-ligand 1 (PD-L1), 54,125 or metabolites such as nitric oxide or prostaglandin E2/cyclooxygenase-2 (PGE 2 /COX-2) in mice, [126][127][128] remodeling of the germinal center, and the focused interaction of B cells, antigen and T FH that drives B cell selection and high-affinity germinal center output. 31 Taken together, both studies highlight that FRC subset specification is transcriptionally and spatially poised in the steady-state to steer efficient adaptive immunity.…”

Untangling Local Pro-Inflammatory, Reparative, and Regulatory Damage-Associated Molecular-Patterns (DAMPs) Pathways to Improve Transplant Outcomes

“…Immunological niches typically provide a hospitable place that concentrates the signals needed to nurture the immune and stromal cells need to maintain an effective local immune response or local homeostasis. An organized immunological microenvironment, or niche, controls local immune responses during tumor development, is necessary for regulating immune cell functions in the secondary lymphoid organs, and fundamental to the production of blood cells in the bone marrow ( 176 – 178 ). We briefly discussed how HA-rich niches in the adventitia are critical for the homeostatic maintenance of vessel function and how these can be disrupted through the loss of specific cells like CCR2 - macrophages or local environmental signals like HA.…”