Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

Allo, Verónica Candela Martínez; Hauk, Vanesa; Sarbia, Nicolás; Pinto, Nicolás A.; Croci, Diego O.; Dalotto-Moreno, Tomás; Morales, Rosa María; Gatto, Sabrina; Cocco, Montana N Manselle; Stupirski, Juan C.; Deladoey, Ángel; Maronna, Esteban; Marcaida, Priscila; Durigan, Virginia; Secco, Anastasia; Mamani, Marta; Santos, A. Dos; Pellet, Antonio Catalán; Leirós, Claudia Pérez; Rabinovich, Gabriel A.; Toscano, Marta A.

doi:10.1073/pnas.1922778117

Cited by 43 publications

(38 citation statements)

References 62 publications

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“…In particular, CD8 + IFNg + T and CD8 + PD-1 + T cell infiltration was higher. Consistent with the higher expression of CXCL9 and CXCL10 in submandibular glands, CD8 + CXCR3 + T cells' infiltration increased as well, compared with WT mice (36). It suggested that CTLs could be actively recruited into this target organ.…”

Section: Distribution Of Ctls In the Major Salivary Glandssupporting

confidence: 56%

CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

et al. 2021

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Primary Sjögren’s syndrome (pSS) is a chronic autoimmune disease associated with damage to multiple organs and glands. The most common clinical manifestations are dry eyes, dry mouth, and enlarged salivary glands. Currently, CD4+ T lymphocytes are considered to be key factors in the immunopathogenesis of pSS, but various studies have shown that CD8+ T lymphocytes contribute to acinar injury in the exocrine glands. Therefore, in this review, we discussed the classification and features of CD8+ T lymphocytes, specifically describing the role of CD8+ T lymphocytes in disease pathophysiology. Furthermore, we presented treatment strategies targeting CD8+ T cells to capitalize on the pathogenic and regulatory potential of CD8+ T lymphocytes in SS to provide promising new strategies for this inflammatory disease.

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Section: Distribution Of Ctls In the Major Salivary Glandssupporting

confidence: 56%

CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

et al. 2021

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“…We demonstrated that aged Lgals1 -/mice had lower expression of PD-L1 in salivary gland cells and increased recruitment of IFN-γ-producing PD-1 + CD8 + T cells to this organ. Moreover, Gal-1-deficient mice showed higher frequency of DCs with immunogenic capacity [93]. We verified these findings in nonobese diabetic (NOD) mice, a well-established mouse model for Sjögren's-like syndrome.…”

Section: Sjögren's Syndromesupporting

confidence: 70%

“…Sjögren's syndrome is characterized by lymphocytic infiltration of exocrine glands and the presence of different autoantibodies. In contrast to CIA and EAE models, where mice were immunized with arthritogenic and encephalitogenic peptides, mice lacking Gal-1 or complex branched N-glycans developed spontaneous age-dependent sialadenitis resembling Sjögren's syndrome manifestations [93]. Lack of Gal-1 disrupted tolerogenic circuits and enhanced T cell activation and recruitment to the salivary glands.…”

Section: Sjögren's Syndromementioning

confidence: 99%

“…In this section, we will focus on the role of Gal-1 in regulating immune tolerance and suppressing inflammation in different models of autoimmune disease. The immunosuppressive properties of Gal-1 have been evaluated in several diseases and experimental models of chronic inflammation and autoimmunity, including experimental autoimmune encephalomyelitis (EAE) [49], collagen-induced arthritis (CIA) [91,92], Sjögren's syndrome [93], 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis [94], celiac disease [88], experimental autoimmune uveitis (EAU), experimental induced uveitis (EIU) [95,96], experimental autoimmune diabetes [97,98], experimental autoimmune orchitis (EAO) [99] and allergic airway inflammation [100].…”

Section: Gal-1: a Potential Therapeutic Agent For Autoimmune And Chronic Inflammatory Diseasesmentioning

confidence: 99%

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Recalibrating Immunity in Cancer and Autoimmune Inflammation by Galectin-1-Driven Regulatory Circuits

Bach¹,

Cutine²,

Laporte³

et al. 2020

scirevfew

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Endogenous lectins play key roles in cell homeostasis by decoding the information encrypted in glycans present on the cell surface or extracellular matrix. Galectins, a family of soluble lectins, have emerged as central regulators of innate and adaptive immune responses. In this article, we review seminal work demonstrating the immunoregulatory roles of Galectin-1 (Gal-1), a proto-type member of the galectin family, and highlight central mechanisms that control its functions in cancer and autoimmune inflammation. Understanding the cellular pathways that control Gal-1 expression and function in tumor and inflammatory microenvironments will set the bases for the design of rational therapies based on positive or negative modulation of this endogenous lectin in cancer and autoimmune diseases.

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“…Consistent with this possibility, we observed the presence of a tolerogenic gene module of 30 genes, including IDO1 , LAMTOR1, IL4L1 and LGALS1, expressed by LCs. Galectin-1 encoded by the LGALS1 gene has been shown to promote the generation of tolerogenic DCs and to enable Tr1 type Tregs to supress Th1- and Th17-mediated inflammation 46,46 . Thus, Galectin-1 secreted by LCs could function in an autocrine as well as paracrine manner to promote Treg responses.…”

Section: Discussionmentioning

confidence: 99%

Langerhans cells immunocompetency is critical for IDO1-dependent ability to induce tolerogenic T cells

Davies

Sirvent

Vallejo

et al. 2019

Preprint

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Human epidermal Langerhans cells (LCs) can coordinate both immunogenic and tolerogenic immune responses, creating an attractive opportunity for immunomodulation strategies. To investigate transcriptional determinants of human primary LC tolerance we applied single cells RNA-sequencing combined with extensive functional analysis. Unsupervised clustering of single cell transcriptomes indicated that steady-state LC populations exist in a spectrum of immune activation between two states: immunocompetent and immature, distinguishable by high or low CD86 expression, respectively. Suprisingly, LC immunompetency was critical for the efficient induction of regulatory T cells during co-culture assays with naïve CD4+ T cells and expansion of autologous memory T cells. Consistently, LC tolerogenic potential was significantly enhanced upon migration from the epidermis. Transcriptional programmes underpinning LC immunocompetency, with increased expression of dendritic cell activation markers (CD83, HLA-DRA and CCR7), were complemented with expression of tolerogenic markers (IDO1, LGALS1 and AHR) in migrated LC. Using protein expression analysis and perturbation with inhibitors, we confirmed the role of IDO1 as a key regulator of LC tolerogenic responses induced during LC migration, identified AHR as a potential component of IDO1-regulatory feedback loop, and demonstrated LC-mediated tolerance can be modulated through treatment with dexamethasone, indicating an opportunity for targeted therapeutic interventions in inflammatory skin disease.

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Suppression of age-related salivary gland autoimmunity by glycosylation-dependent galectin-1-driven immune inhibitory circuits

Cited by 43 publications

References 62 publications

CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

CD8+ T Lymphocytes: Crucial Players in Sjögren’s Syndrome

Recalibrating Immunity in Cancer and Autoimmune Inflammation by Galectin-1-Driven Regulatory Circuits

Langerhans cells immunocompetency is critical for IDO1-dependent ability to induce tolerogenic T cells

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