Nonredundant Roles of Sema4A in the Immune System: Defective T Cell Priming and Th1/Th2 Regulation in Sema4A-Deficient Mice

Kumanogoh, Atsushi; Shikina, Takashi; Suzuki, Kazuhiro; Uematsu, Satoshi; Yukawa, Kazunori; Kashiwamura, Shin-ichiro; Tsutsui, Hiroko; Yamamoto, Midori; Takamatsu, Hyota; Ko-Mitamura, Elizabeth P.; Takegahara, Noriko; Marukawa, Satoko; Ishida, Isao; Morishita, Hiroshi; Prasad, Durbaka V. R.; Tamura, Manabu; Mizui, Masayuki; Toyofuku, Toshihiko; Akira, Shizuo; Takeda, Kiyoshi; Okabe, Masaru; Kikutani, Hitoshi

doi:10.1016/j.immuni.2005.01.014

Cited by 151 publications

(180 citation statements)

References 32 publications

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“…Conversely, Sema4A-deficient mice show enhanced T-helper type 2 (Th2) responses against Nippostrongylus brasiliensis, a Th2-inducing intestinal nematode. 53 TIM-2, a negative regulator of Th2 cells, 54 has been suggested to serve as a functional receptor for Sema4A. 30 Consistent with these findings, TIM-2 is preferentially upregulated on Th2 cells.…”

Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 84mentioning

confidence: 64%

“…Sema4A is constitutively expressed in DCs and induced in polarized T-helper type 1 (Th1) cells. 30,53 DC-derived Sema4A is crucial for antigen-specific T-cell priming via T cell-DC-cognate cell interactions, while T cell-derived Sema4A is involved in helper T-cell differentiation via T cell-T cell cognate cell interactions. Indeed, Sema4A-deficient mice have impaired Th1 responses to heat-killed Propionibacterium acnes, a Th1-inducing bacteria.…”

Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 84mentioning

confidence: 99%

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Regulation of immune cell responses by semaphorins and their receptors

2010

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Semaphorins were originally identified as axon guidance factors involved in the development of the neuronal system. However, accumulating evidence indicates that several members of semaphorins, so-called 'immune semaphorins', are crucially involved in various phases of immune responses. These semaphorins regulate both immune cell interactions and immune cell trafficking during physiological and pathological immune responses. Here, we review the following two functional aspects of semaphorins and their receptors in immune responses: their functions in cell-cell interactions and their involvement in immune cell trafficking.

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Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 84mentioning

confidence: 64%

Section: Regulation Of Immune Cell Responses H Takamatsu Et Al 84mentioning

confidence: 99%

Regulation of immune cell responses by semaphorins and their receptors

2010

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“…On the other hand, knock-out mouse models generated in H. Kikutani's lab have clearly demonstrated that class 4 semaphorins Sema4D and Sema4A regulate the immune response mediated by lymphocytes and dendritic cells. 60,61 Interestingly, PlexinA1 was shown to have a role in the "adhesion" between lymphocytes and regulatory cells 62 (the so called "immunological synapse"), inviting the idea that semaphorins could police this association. This matter is reviewed in detail in an associated review.…”

Section: Leucocyte Migrationmentioning

confidence: 99%

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

Casazza¹,

Fazzari²,

Tamagnone

2007

Advances in Experimental Medicine and Biology

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C ell migration is pivotal in embryo development and in the adult. During development, a wide range of progenitor cells travel over long distances before undergoing terminal differentiation. Moreover, the morphogenesis of epithelial tissues and of the cardio-vascular system involves remodelling compact cell layers and the sprouting of new tubular branches. In the adult, cell migration is essential for the leucocytes involved in immune response. Furthermore, invasive and metastatic cancer cells have the distinctive ability to overcome normal tissue boundaries, travel in and out the blood vessels, and settle down in heterologous tissues. Cell migration normally follows strict guidance cues, either attractive, or inhibitory and repulsive. Semaphorins are a wide family of signals guiding cell migration during development and in the adult. Recent findings have established that semaphorin receptors, the plexins, govern cell migration by regulating integrin-based cell substrate adhesion and actin cytoskeleton dynamics, via specific monomeric GTPases. Plexins furthermore recruit tyrosine kinases in receptor complexes, which allows switching between multiple signalling pathways and functional outcomes. In this article, we will review the functional role of semaphorins in cell migration and the implicated molecular mechanisms controlling cell adhesion.

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“…However, cumulative findings indicate that semaphorins have diverse functions in many physiological processes (18)(19)(20)(21)(22). Semaphorins have been shown to be involved in various phases of immune responses, including the activation of B cells (23), T cells (24), and dendritic cells (DCs) (25); the regulation of Th differentiation (26); and the navigation of immune cell trafficking (27). In particular, membrane-bound class IV semaphorins, Sema4A and Sema4D/CD100, have been extensively investigated.…”

mentioning

confidence: 99%

“…Sema4D has been shown to be important for B cell and DC activation (23). In addition, Sema4A has been demonstrated to be critical for Th differentiation (26). However, the impact of other class IV semaphorins on other immune functions has not been determined.…”

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confidence: 99%

Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses

Nakagawa

Takamatsu

Okuno

et al. 2011

The Journal of Immunology

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Basophils are strong mediators of Th2 responses during helminthic infections. Recently, basophils were shown to function as APCs and promote both Th2 skewing and humoral memory responses. However, the mechanisms that regulate basophils are still unclear. In this article, we show that a class IV semaphorin, Sema4B, negatively regulates basophil functions through T cell–basophil contacts. In a screen to identify semaphorins that function in the immune system, we determined that Sema4B is expressed in T and B cells. Interestingly, Sema4B−/− mice had considerably increased serum IgE levels despite normal lymphocyte and dendritic cell functions. Recombinant Sema4B significantly inhibited IL-4 and IL-6 production from basophils in response to various stimuli, including IL-3, papain, and FcεRI cross-linking. In addition, T cell-derived Sema4B, which accumulated at contact sites between basophils and CD4+ T cells, suppressed basophil-mediated Th2 skewing, suggesting that Sema4B regulates basophil responses through cognate cell–cell contacts. Furthermore, Sema4B−/− mice had enhanced basophil-mediated memory IgE production, which was abolished by treating with an anti-FcεRIα Ab. Collectively, these results indicate that Sema4B negatively regulates basophil-mediated Th2 and humoral memory responses.

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Nonredundant Roles of Sema4A in the Immune System: Defective T Cell Priming and Th1/Th2 Regulation in Sema4A-Deficient Mice

Cited by 151 publications

References 32 publications

Regulation of immune cell responses by semaphorins and their receptors

Regulation of immune cell responses by semaphorins and their receptors

Semaphorin Signals in Cell Adhesion and Cell Migration: Functional Role and Molecular Mechanisms

Identification of Semaphorin 4B as a Negative Regulator of Basophil-Mediated Immune Responses

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