The protozoan commensal Tritrichomonas musculis is a natural adjuvant for mucosal IgA.

Immunoglobulin (Ig) A supports mucosal immune homeostasis and host-microbiota interactions. While commensal bacteria are known for their ability to promote IgA, the role of non-bacterial commensal microbes in the induction of IgA remains elusive. Here, we demonstrate that permanent colonization with the protozoan commensal Tritrichomonas musculis (T.

Neonatal LTβR signaling is required for the accumulation of eosinophils in the inflamed adult mesenteric lymph node.

Although eosinophils are important contributors to mucosal immune responses, mechanisms that regulate their accumulation in mucosal-associated lymphoid tissues remain ill-defined. Combining bone marrow chimeras and pharmacological inhibition approaches, here we find that lymphotoxin-beta receptor (LTβR) signaling during the neonatal period is required for the accumulation of eosinophils in the mesenteric lymph nodes (MLN) during an enteric viral infection in adult male and female mice. We demonstrate that MLN stromal cells express genes that are important for eosinophil migration and survival, such as Ccl-11 (eotaxin-1), Ccl7, Ccl9, and Cxcl2, and that expression of most of these genes is downregulated as a consequence of neonatal LTβR blockade.

CCR6 Expression on B Cells Is Not Required for Clinical or Pathological Presentation of MOG Protein-Induced Experimental Autoimmune Encephalomyelitis despite an Altered Germinal Center Response.

B cells have been implicated in the pathogenesis of multiple sclerosis, but the mechanisms that guide B cell activation in the periphery and subsequent migration to the CNS remain incompletely understood. We previously showed that systemic inflammation induces an accumulation of B cells in the spleen in a CCR6/CCL20-dependent manner. In this study, we evaluated the role of CCR6/CCL20 in the context of myelin oligodendrocyte glycoprotein (MOG) protein-induced (B cell-dependent) experimental autoimmune encephalomyelitis (EAE).

Lymph node stromal CCL2 limits antibody responses.

Nonhematopoietic stromal cells in lymph nodes such as fibroblastic reticular cells (FRCs) can support the survival of plasmablasts and plasma cells [together, antibody-forming cells (AFCs)]. However, a regulatory function for the stromal compartment in AFC accumulation has not been appreciated. Here, we show that chemokine ligand 2 (CCL2)-expressing stromal cells limit AFC survival.

A protective Langerhans cell-keratinocyte axis that is dysfunctional in photosensitivity.

Photosensitivity, or skin sensitivity to ultraviolet radiation (UVR), is a feature of lupus erythematosus and other autoimmune and dermatologic conditions, but the mechanistic underpinnings are poorly understood. We identify a Langerhans cell (LC)-keratinocyte axis that limits UVR-induced keratinocyte apoptosis and skin injury via keratinocyte epidermal growth factor receptor (EGFR) stimulation. We show that the absence of LCs in Langerin-diphtheria toxin subunit A (DTA) mice leads to photosensitivity and that, in vitro, mouse and human LCs can directly protect keratinocytes from UVR-induced apoptosis.

Tertiary lymphoid organs in systemic autoimmune diseases: pathogenic or protective?

Tertiary lymphoid organs are found at sites of chronic inflammation in autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. These organized accumulations of T and B cells resemble secondary lymphoid organs and generate autoreactive effector cells. However, whether they contribute to disease pathogenesis or have protective functions is unclear.

Dendritic cells maintain dermal adipose-derived stromal cells in skin fibrosis.

Scleroderma is a group of skin-fibrosing diseases for which there are no effective treatments. A feature of the skin fibrosis typical of scleroderma is atrophy of the dermal white adipose tissue (DWAT). Adipose tissue contains adipose-derived mesenchymal stromal cells (ADSCs) that have regenerative and reparative functions; however, whether DWAT atrophy in fibrosis is accompanied by ADSC loss is poorly understood, as are the mechanisms that might maintain ADSC survival in fibrotic skin.

Regulation of Lymph Node Vascular-Stromal Compartment by Dendritic Cells.

During normal and pathologic immune responses, lymph nodes can swell considerably. The lymph node vascular-stromal compartment supports and regulates the developing immune responses and undergoes dynamic expansion and remodeling. Recent studies have shown that dendritic cells (DCs), best known for their antigen presentation roles, can directly regulate the vascular-stromal compartment, pointing to a new perspective on DCs as facilitators of lymphoid tissue function.

A dendritic-cell-stromal axis maintains immune responses in lymph nodes.

Within secondary lymphoid tissues, stromal reticular cells support lymphocyte function, and targeting reticular cells is a potential strategy for controlling pathogenic lymphocytes in disease. However, the mechanisms that regulate reticular cell function are not well understood. Here we found that during an immune response in lymph nodes, dendritic cells (DCs) maintain reticular cell survival in multiple compartments.

Multiple CD11c+ cells collaboratively express IL-1β to modulate stromal vascular endothelial growth factor and lymph node vascular-stromal growth.

Lymphadenopathy in autoimmune and other lymphoproliferative diseases is in part characterized by immunoblasts and vascular proliferation. The lymph node vasculature, along with the nonvascular stromal compartment, supports lymphocyte function, and targeting vascular-stromal expansion in inflamed nodes may modulate lymphocyte function in disease. CD11c(+) cells are essential for vascular-stromal proliferation and the upregulation of vascular endothelial growth factor (VEGF) needed for vascular proliferation.