Impaired Regulation by IL-35 in Systemic Sclerosis

Osuna-Gómez, Rubén; Castellví, Iván; Mulet, Maria; Ortiz, Ma Àngels; Brough, Douglas E.; Sabzevari, Helen; Semnani, Roshanak Tolouei; Vidal, Sílvia

doi:10.3390/ijms241310567

Cited by 2 publications

(3 citation statements)

References 48 publications

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“…Invariably, IL-35 has been linked with disease pathogenesis and poor survival in mouse models of chronic inflammatory diseases or cancers and similar correlations were made in patients [33][34][35][36][37] . IL-35 exerts an immunosuppressive effect by inhibiting B/T cells, dendritic cells, and type 1 macrophages [25][26][27][38][39][40][41] and by promoting, expanding, and activating immunoregulatory cells 26,28,29,32,39,[42][43][44] , and also facilitates tumor angiogenesis 45,46 . However, the effects of IL-35 on primary NK cells have never been characterized.…”

Section: Introductionmentioning

confidence: 99%

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Bendriss-Vermare,

Picant,

Revol-Bauz

et al. 2024

Preprint

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Natural Killer (NK) cells lose their effector functions towards dangerous cells in chronic inflammatory diseases through still elusive mechanisms. Here, we demonstrate that Interleukin 35 (IL-35), an immunosuppressive member of the IL-12 family, inhibits human NK cell proliferation, pro-inflammatory, and cytotoxic functions, while promoting their secretion of TGF-β and proangiogenic factors. Furthermore, prolonged exposure to IL-35 converts NK cells into ILC1-like cells with tissue residency features (CD9+CD103+CD49a+) and low effector functions, that was dependent on autocrine TGF-β. Single cell RNAseq analysis also revealed an ILC1-like heterogeneity associated to the initial NK subpopulation, conventional or adaptive, undergoing the conversion. Overall, our findings identify a new role of IL-35 as a key driver of NK cell plasticity leading to the acquisition of tissue residency features and weakened effector functions that might play a role in physiopathological contexts and represent an attractive target for future immunotherapies to improve NK cell clinical activity.

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Section: Introductionmentioning

confidence: 99%

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Bendriss-Vermare,

Picant,

Revol-Bauz

et al. 2024

Preprint

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“… 11–13 , 21 Some authors noted low levels of IL-35 in patients with SSc, while for TGFβ, IL-10 and IL −17 increased plasma levels were recorded. 22 …”

Section: Introductionmentioning

confidence: 99%

“…[11][12][13]21 Some authors noted low levels of IL-35 in patients with SSc, while for TGFβ, IL-10 and IL −17 increased plasma levels were recorded. 22 Although the pathogenesis of SSc is partially known, it is still not clear how this disease begins. 4,[23][24][25] Peripheral microvasculopathy is the result of defective angiogenesis that induces cellular hypoxia by reducing blood flow.…”

Section: Introductionmentioning

confidence: 99%

The Association of Telangiectasias with Other Peripheral Vascular Lesions of Systemic Sclerosis

Bobeica,

Niculet,

Musat

et al. 2024

CCID

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Purpose Systemic sclerosis (SSc) is a relatively rare collagenosis manifested as microvasculopathy, excessive cutaneous and visceral fibrosis in a background of autoimmune alteration. Autoimmune vasculopathy in SSc occurs early and begins with endothelial cell activation followed by blood vessel intimal proliferation in a context of defective angiogenesis. The alteration of peripheral micro and macrocirculation in SSc is evident through vascular lesions, such as Raynaud’s phenomenon, telangiectasias, acrocyanosis, digital ulcers, gangrene, peripheral pulse deficiency. Our paper details the results of the study on the association between telangiectasias and other types of immune-mediated peripheral vascular lesions that can be identified in SSc. The presence of these peripheral vascular lesions can provide information about the magnitude of the peripheral vasculopathy. Patients and Methods A total of 37 patients diagnosed with SSc, recruited from a university clinic in Bucharest between February 2019 and March 2020, were enrolled in an observational study. We evaluated the presence of telangiectasias, as a stigma of autoimmune microvasculopathy, and their association with other immune-mediated peripheral vascular lesions that may be present in SSc. Results The presence of telangiectasias was identified in the absence, but especially in the presence of acrocyanosis and digital ulcerations, and patients with peripheral pulse deficiency almost always had telangiectasias. Less than a quarter of the patients with digital ulcers progressed unfavorably to gangrene, and only one required amputation, telangiectasias being present not only in the patient with amputation but in all patients with gangrene. Conclusion We appreciate that telangiectasias may be the clinical expression of peripheral vasculopathy characteristic of SSc, they can often be present in association with other peripheral vascular lesions and may represent a valuable indicator for the gangrene risk of digital ulcerations in SSc.

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Impaired Regulation by IL-35 in Systemic Sclerosis

Cited by 2 publications

References 48 publications

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

Interleukin-35 impairs human NK cell effector functions and induces their ILC1-like conversion with tissue residency features

The Association of Telangiectasias with Other Peripheral Vascular Lesions of Systemic Sclerosis

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