SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses

Knosp, Camille; Carroll, Helen P.; Elliott, J.; Saunders, Sean P.; Nel, Hendrik J.; Amu, Sylvie; Pratt, Joanne C.; Spence, Shaun; Doran, Emma; Cooke, Nicola; Jackson, Ruaidhrí; Swift, J.; Fitzgerald, Denise; Heaney, Liam G.; Fallon, Padraic G.; Kissenpfennig, Adrien; Johnston, James A.

doi:10.1084/jem.20101167

Cited by 75 publications

(83 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Collectively, our data demonstrate that Socs2 2/2 iTregs failed to maintain Foxp3 expression when stimulated with IL-4 and constitutively secreted IFN-g. Of note, the fact that Socs2 2/2 CD4 + T cells secreted significantly higher IL-4 compared with WT CD4 + T cells may accelerate this process, both in in vitro and in vivo systems (16).…”

Section: Il-4 Mediates Socs2mentioning

confidence: 99%

“…Spleen, lymph nodes (LN), and thymus were aseptically removed from mice, and single-cell suspensions were prepared, as previously described (16). Intact small intestine was extracted, cleaned, and dissected.…”

Section: Preparation Of Lymphocyte Cell Suspensionsmentioning

confidence: 99%

“…2/2 mice present with normal CD4 + T cell development (16,31). Interestingly, several groups have since characterized the Foxp3 + Treg transcriptome and revealed that SOCS2 is prefer-entially expressed in Foxp3 + Treg cells compared with other T cell subsets, both in the thymus and in the periphery (23)(24)(25) + cells in two groups of age-and sex-matched mice (WT n = 7-10; Socs2 2/2 n = 6-8).…”

Section: Socs2mentioning

confidence: 99%

“…Recent studies implicate SOCS proteins as likely candidates to control differentiation of immune cells and thus help to shape the type of inflammatory response (12,13). Importantly, SOCS proteins appear to modulate CD4 + T cell polarization (14); this is exemplified by the differentiation of Th2 cells being regulated by SOCS3 and SOCS2 (15,16), whereas Th17 differentiation has been shown to be regulated by SOCS1 and SOCS3 (17,18).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Regulation of Foxp3+ Inducible Regulatory T Cell Stability by SOCS2

Knosp

Schiering

Spence

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Suppressor of cytokine signaling (SOCS) proteins are key regulators of CD4+ T cell differentiation, and in particular, we have recently shown that SOCS2 inhibits the development of Th2 cells and allergic immune responses. Interestingly, transcriptome analyses have identified SOCS2 as being preferentially expressed in both natural regulatory T cells (Tregs) and inducible Tregs (iTregs); however, the role of SOCS2 in Foxp3+ Treg function or development has not been fully elucidated. In this study, we show that despite having no effect on natural Treg development or function, SOCS2 is highly expressed in iTregs and required for the stable expression of Foxp3 in iTregs in vitro and in vivo. Indeed, SOCS2-deficient CD4+ T cells upregulated Foxp3 following in vitro TGF-β stimulation, but failed to maintain stable expression of Foxp3. Moreover, in vivo generation of iTregs following OVA feeding was impaired in the absence of SOCS2 and could be rescued in the presence of IL-4 neutralizing Ab. Following IL-4 stimulation, SOCS2-deficient Foxp3+ iTregs secreted elevated IFN-γ and IL-13 levels and displayed enhanced STAT6 phosphorylation. Therefore, we propose that SOCS2 regulates iTreg stability by downregulating IL-4 signaling. Moreover, SOCS2 is essential to maintain the anti-inflammatory phenotype of iTregs by preventing the secretion of proinflammatory cytokines. Collectively, these results suggest that SOCS2 may prevent IL-4–induced Foxp3+ iTreg instability. Foxp3+ iTregs are key regulators of immune responses at mucosal surfaces; therefore, this dual role of SOCS2 in both Th2 and Foxp3+ iTregs reinforces SOCS2 as a potential therapeutic target for Th2-biased diseases.

show abstract

Section: Il-4 Mediates Socs2mentioning

confidence: 99%

Section: Preparation Of Lymphocyte Cell Suspensionsmentioning

confidence: 99%

Section: Socs2mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Foxp3+ Inducible Regulatory T Cell Stability by SOCS2

Knosp

Schiering

Spence

et al. 2013

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

show abstract

“…ограничивая провоспалительную активацию анти-генпрезентирующих клеток, а также натуральных киллеров (NK) [6][7][8][9]. Таким образом, состояние JAK/STAT-сигнального пути определяет эффективность про-цессов пролиферации, дифференцировки, роста, противовирусного ответа и т.д.…”

unclassified

The state of receptor-dependent signal pathways in the agranulocytes from the peripheral blood of the reconvalescent patients following community-acquired pneumonia under the influence of microwave radiation

Терехов

Бондарь

Хадарцев

2016

Vopr. kurortol. fizioter. lech. fiz. kul't.

View full text Add to dashboard Cite

A computer vision approach to rare cell in vivo fluorescence flow cytometry

Markovic

Pera

et al. 2013

Cytometry Pt A

View full text Add to dashboard Cite

Non-invasive enumeration of rare circulating cell populations in small animals is of great importance in many areas of biomedical research. In this work we describe a macroscopic fluorescence imaging system and automated computer vision algorithm that allows in vivo detection, enumeration and tracking of circulating fluorescently-labeled cells from multiple large blood vessels in the ear of a mouse. This imaging system uses a 660 nm laser and a high sensitivity electron-multiplied charge coupled device camera (EMCCD) to acquire fluorescence image sequences from relatively large (~5 × 5 mm2) imaging areas. The primary technical challenge was developing an automated method for identifying and tracking rare cell events in image sequences with substantial autofluorescence and noise content. To achieve this, we developed a two-step image analysis algorithm that first identified cell candidates in individual frames, and then merged cell candidates into tracks by dynamic analysis of image sequences. The second step was critical since it allowed rejection of >97% of false positive cell counts. Overall, our computer vision IVFC (CV-IVFC) approach allows single-cell detection sensitivity at estimated concentrations of 20 cells per mL of peripheral blood. In addition to simple enumeration, the technique recovers the cell’s trajectory, which in the future could be used to automatically identify, for example, in vivo homing and docking events.

show abstract

SOCS2 regulates T helper type 2 differentiation and the generation of type 2 allergic responses

Abstract: SOCS2-deficient T cells more readily produce Th2 cytokines, and SOCS2-deficient mice exhibit exacerbated atopic dermatitis and allergic airway inflammation.

Cited by 75 publications

References 36 publications

Regulation of Foxp3+ Inducible Regulatory T Cell Stability by SOCS2

Regulation of Foxp3+ Inducible Regulatory T Cell Stability by SOCS2

The state of receptor-dependent signal pathways in the agranulocytes from the peripheral blood of the reconvalescent patients following community-acquired pneumonia under the influence of microwave radiation

A computer vision approach to rare cell in vivo fluorescence flow cytometry

Contact Info

Product

Resources

About