Paula Licona-Limon

• PhD
• Professor (Associate) at National Autonomous University of Mexico

Type 2 inflammatory cytokines, including interleukin-4 (IL-4), IL-5, IL-9, and IL-13, drive the characteristic features of immunity against parasitic worms and allergens. Whether IL-9 serves an essential role in the initiation of host-protective responses is controversial, and the importance of IL-9- versus IL-4-producing CD4(+) effector T cells in...

The initiation of type 2 immune responses by the epithelial cell-derived cytokines IL-25, IL-33 and TSLP has been an area of extensive research in the past decade. Such studies have led to the identification of a new innate lymphoid subset that produces the canonical type 2 cytokines IL-5, IL-9 and IL-13 in response to IL-25 and IL-33. These group...

CD4(+) type 1 T regulatory (Tr1) cells are induced in the periphery and have a pivotal role in promoting and maintaining tolerance. The absence of surface markers that uniquely identify Tr1 cells has limited their study and clinical applications. By gene expression profiling of human Tr1 cell clones, we identified the surface markers CD49b and lymp...

Regulation of metabolic pathways in the immune system provides a mechanism to actively control cellular function, growth, proliferation, and survival. Here, we report that miR-181 is a nonredundant determinant of cellular metabolism and is essential for supporting the biosynthetic demands of early NKT cell development. As a result, miR-181-deficien...

Transforming growth factor-beta (TGFbeta) is an immunosuppressive cytokine produced by tumour cells and immune cells that can polarize many components of the immune system. This Review covers the effects of TGFbeta on natural killer (NK) cells, dendritic cells, macrophages, neutrophils, CD8(+) and CD4(+) effector and regulatory T cells, and NKT cel...

The mechanisms that negatively regulate inflammation upon a pathogenic stimulus are crucial for the maintenance of tissue integrity and organ function. T regulatory cells are one of the main drivers in controlling inflammation. The ability of Treg cells to adapt to different inflammatory cues and suppress inflammation is one of the relevant feature...

Bystander activation that leads to expression of IL-9 in effector TH9 cells is induced by a TCR-independent, STAT-dependent mechanism and may represent a new strategy for therapeutic intervention to treat TH9-induced pathologies in vivo.

Although IL-9 has potent anti-tumor activity in adoptive cell transfer therapy, some models suggest that it can promote tumor growth. Here, we show that IL-9 signaling is associated with poor outcomes in patients with various forms of lung cancer, and is required for lung tumor growth in multiple mouse models. CD4+ T cell-derived IL-9 promotes the...

[This corrects the article DOI: 10.3389/fimmu.2017.00441.].

Type 2 Innate lymphoid cells (ILC2s) are tissue-resident immune cells activated by epithelial-derived alarmins upon tissue damage. They regulate immunity against helminth parasites and allergies by expressing type 2 immune response cytokines including IL-9, known to be critical for inducing and potentiating the immune response in such context. Alth...

The process by which blood cells are generated has been widely studied in homeostasis and during pathogen-triggered inflammatory response. Recently, murine lungs have been shown to be a significant source of hematopoietic progenitors in a process known as extramedullary hematopoiesis. Using multiparametric flow cytometry, we have identified mesench...

Asthma is a chronic inflammatory lung disease with intermittent flares predominately mediated through memory T cells. Yet, the identity of long-term memory cells that mediate allergic recall responses is not well defined. In this report, using a mouse model of chronic allergen exposure followed by an allergen-free rest period, we characterized a su...

Despite IL-9 functioning as a pleiotropic cytokine in mucosal environments, the IL-9–responsive cell repertoire is still not well defined. Here, we found that IL-9 mediates proallergic activities in the lungs by targeting lung macrophages. IL-9 inhibits alveolar macrophage expansion and promotes recruitment of monocytes that develop into CD11c ⁺ an...

Acute lymphocytic leukemia is the most common type of cancer in pediatric individuals. Glucose regulated protein (GRP78) is an endoplasmic reticulum chaperone that facilitates the folding and assembly of proteins and regulates the unfolded protein response pathway. GRP78 has a role in survival of cancer and metastasis and cell-surface associated GR...

Innate lymphoid cells (ILCs) are the most recently described group of lymphoid subpopulations. These tissue-resident cells display a heterogeneity resembling that observed on different groups of T cells, hence their categorization as cytotoxic NK cells and helper ILCs type 1, 2 and 3. Each one of these groups is highly diverse and expresses differe...

In cutaneous T cell lymphoma (CTCL), a dominant Th2 profile associated with disease progression has been proposed. Moreover, although the production and regulation of IL-4 expression during the early stages of the disease may have important implications in later stages, these processes are poorly understood. Here, we demonstrate the presence of TOX...

Tissue-resident innate lymphoid cells (ILCs) help sustain barrier function and respond to local signals. ILCs are traditionally classified as ILC1, ILC2 or ILC3 on the basis of their expression of specific transcription factors and cytokines¹. In the skin, disease-specific production of ILC3-associated cytokines interleukin (IL)-17 and IL-22 in res...

Background: We have previously identified IL-9 producing mucosal mast cell (MMC9) as the primary source of IL-9 to drive intestinal mastocytosis and experimental IgE-mediated food allergy. However, the molecular mechanisms that regulate the expansion of MMC9s remain unknown. Objective: We hypothesized that IL-4 regulates MMC9 development and MMC...

TH17 cells exemplify environmental immune adaptation: they can acquire both a pathogenic and an anti-inflammatory fate. However, it is not known whether the anti-inflammatory fate is merely a vestigial trait, or whether it serves to preserve the integrity of the host tissues. Here we show that the capacity of TH17 cells to acquire an anti-inflammat...

Generation of allelic gene reporter mice has provided a powerful tool to study gene function in vivo. In conjunction with imaging technologies, reporter mouse models facilitate studies of cell lineage tracing, live cell imaging, and gene expression in the context of diseases. Although there are several advantages to using reporter mice, caution is...

Adaptive immunity provides life-long protection by generating central and effector memory T cells and the most recently described tissue resident memory T (TRM) cells. However, the cellular origin of CD4 TRM cells and their contribution to host defense remain elusive. Using IL-17A tracking-fate mouse models, we found that a significant fraction of...

As current levels of antimicrobial resistance are alarming, the World Health Organization urged the development of new antimicrobials to fight infections produced by multidrug resistant bacteria. Antibiotics impose severe selective pressure for the development of resistance, and currently bacteria resistant to all of them exist. In this review, we...

Hematopoiesis is a highly regulated process and it’s widely described in bone marrow, the classical niche for hematopoietic stem cells (HSCs). The lungs are a novel niche of HSCs, as recently described by Lefrançais in 2017, however, little is known about the nature of these cells. Isthmin 1 (ISM1) is a secreted molecule important in developmental...

Psoriasis pathology is driven by the type 3 cytokines IL-17 and Il-22, but little is understood about the dynamics that initiate alterations in tissue homeostasis. Here, we use mouse models, single-cell RNA-seq (scRNA-seq), computational inference and cell lineage mapping to show that psoriasis induction reconfigures the functionality of skin-resid...

Early life stress (ELS) affects hippocampal neurogenesis, increases depressive-like behavior, and causes mild metabolic imbalance in early adulthood (2 months). However, whether these effects worsen in mid life remains unclear. To test whether age-dependent effects of ELS on hippocampal neurogenesis are related to deficient hypothalamic-pituitary-a...

In the last decade, growing evidence has shed some light into an unrecognized capacity of the innate immune compartment: the unexpected ability of innate cells to enhance its response upon an immunological re-challenge. This capacity is called Trained immunity and resembles adaptive immune memory but lacks the specificity of antigen recognition by...

Over the years, the study of gene function during development involved the implementation of sophisticated transgenic strategies to visualize how organisms change during their lifetime. These strategies are diverse and extremely useful and allowed the discovery of some of the fundamental mechanisms governing organism’s development. Such strategies...

Local macrophage clean-up Infection, especially by helminths or bacteria, can cause tissue damage (see the Perspective by Bouchery and Harris). Minutti et al. studied mouse models of helminth infection and fibrosis. They expressed surfactant protein A (a member of the complement component C1q family) in the lung, which enhanced interleukin-4 (IL-4)...

Th9 cells are a new subpopulation of CD4+ T helper cells, characterized by the expression of IL-9 that have been involved in type 2 immune responses, antitumor responses and autoimmune diseases. Here, we describe two different parasitic models frequently maintained in the laboratory where Th9 cells or IL-9 (the cytokine produced by Th9 cells) has b...

Acinetobacter baumannii is the etiologic agent of a wide range of nosocomial infections, including pneumonia, bacteremia, and skin infections. Over the last 45 years, an alarming increase in the antibiotic resistance of this opportunistic microorganism has been reported, a situation that hinders effective treatments. In order to develop effective t...

Interleukin-9 is a cytokine classically related to type 2 immune responses whose cellular identity has been recently reevaluated to identify a new specialized T helper subset called Th9 and an innate source referred as innate lymphoid cell type 2. Over the past years, IL-9 has been associated with allergic responses, tumor immunology, and autoimmun...

Germinal center (GC) B cells undergo affinity selection, which depends on interactions with CD4(+) follicular helper T cells (TFH cells). We found that TFH cells progressed through transcriptionally and functionally distinct stages and provided differential signals for GC regulation. They initially localized proximally to mutating B cells, secreted...

Acinetobacter baumannii is an emergent opportunistic bacterial pathogen responsible for recalcitrant infections owing to its high intrinsic tolerance to most antibiotics; therefore, suitable strategies to treat these infections are needed. One plausible approach is the repurposing of drugs that are already in use. Among them, anticancer drugs may b...

Host responses against metazoan parasites or an array of environmental substances elicit type 2 immunity. Despite its protective function, type 2 immunity also drives allergic diseases. The mechanisms that regulate the magnitude of the type 2 response remain largely unknown. Here, we show that genetic ablation of a receptor tyrosine kinase encoded...

Initiation of a thymus-dependent humoral immune response requires interaction of activated B cells and follicular B helper T (Tfh) cells, a specialized subset of CD4 T cells. Differentiation of Tfh cells results in their localization to the B-cell follicle and germinal center (GC) of secondary lymphoid organs and expression of the transcription fac...

Inflammation is a beneficial host response to infection but can contribute to inflammatory disease if unregulated. The Th17 lineage of T helper (Th) cells can cause severe human inflammatory diseases. These cells exhibit both instability (they can cease to express their signature cytokine, IL-17A) and plasticity (they can start expressing cytokines...

The cytokine IL-9, derived primarily from T-helper (Th)-9 lymphocytes, promotes expansion of the Th2 subset and is implicated in the mechanisms of allergic asthma. We hypothesize that IL-9 also plays a role in human allergic contact dermatitis (ACD). To investigate this hypothesis, skin biopsy specimens of positive patch test sites from non-atopic...

CD4(+) T cell differentiation is regulated by specialized antigen-presenting cells. Dendritic cells (DCs) produce cytokines that promote naive CD4(+) T cell differentiation into T helper 1 (Th1), Th17, and inducible T regulatory (iTreg) cells. However, the initiation of Th2 cell responses remains poorly understood, although it is likely that more t...

Food as Reward Why does ice cream taste so good? High-fat foods activate a reward circuit in the brain involving dopamine, a neurotransmitter that regulates pleasure. Overconsumption of high-fat foods is thought to dampen this dopamine-induced reward sensation, leading to compensatory consumption of even more high-fat foods. The mechanisms by which...

TGF-β signaling in T cells is critical for peripheral T-cell tolerance by regulating effector CD4(+) T helper (Th) cell differentiation. However, it is still controversial to what extent TGF-β signaling in Foxp3(+) regulatory T (Treg) cells contributes to immune homeostasis. Here we showed that abrogation of TGF-β signaling in thymic T cells led to...

The tumour microenvironment thwarts conventional immunotherapy through multiple immunologic mechanisms, such as the secretion of the transforming growth factor-β (TGF-β), which stunts local tumour immune responses. Therefore, high doses of interleukin-2 (IL-2), a conventional cytokine for metastatic melanoma, induces only limited responses. To over...

Activins and inhibins are members of the transforming growth factor-beta superfamily that act on different cell types and regulate a broad range of cellular processes including proliferation, differentiation, and apoptosis. Here, we provide the first evidence that activins and inhibins regulate specific checkpoints during thymocyte development. We...

Members of the transforming growth factor beta (TGF-beta) superfamily are soluble factors that regulate a variety of functional responses including proliferation, differentiation, apoptosis and cell cycle, among others, depending not only on the cell type and its differentiation state, but also on the milieu of cytokines present. All three members...

Activins are members of the transforming growth factor-beta (TGFbeta) superfamily, which regulate cell differentiation processes. Here we report the first quantitative analysis of the expression of Activin/Inhibin ligands, type I and II receptors, as well as Smad proteins in fetal (E14-E16) and adult thymic subpopulations. Our data showed that Alk4...

The reporter gene xylE (encoding catechol 2,3-dioxygenase) has been modified for a more rational use in Streptomyces. Two reporter fragments, one containing xylE, and the other containing also the upstream gene xylT (which encodes a soluble ferredoxin), have been constructed to allow precise fusion of regulatory regions to the reporter genes. Ident...