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Faculty Lynn Puddington
Associate Professor of Immunology and Medicine
puddington@nso1.uchc.edu
Areas of Interest:
The overall goal of the research ongoing in my laboratory is to
elucidate the contribution of maternal antigen or immune status in the
susceptibility or resistance to development of allergic airway disease
in offspring. It is evident from epidemiological studies that the risk
for childhood asthma is increased by having a positive family history of
asthma. In particular, allergic sensitization of the newborn is closely
linked to maternal but not to paternal allergies. Our focus is on early
life events (either pre-natal or early post-natal) that can result in T
and B cell tolerance or immunity. Our hypothesis is that the environment
in neonatal mice (determined by maternal immunity or passive transfer of
antigen) is critical to immunological outcome, having life-long
influences on development of immune responsiveness. We are identifying
the cells responsible and the mechanisms by which they dictate
functional commitment of the neonate to the development of, or
protection from, atopy.
One strategy we are undertaking to advance this work is to
characterize the antigen-presenting environment in pre- and post-natal
life, with the focus on defining factors that dictate whether exposure
to allergen in early life induces T cell sensitization or tolerance. The
thinking is that in certain circumstances, T cell sensitization can
occur in utero or in early post-natal life and that factors responsible
for these circumstances have increased in the past 20 years. It has been
proposed that this could explain the increased incidence of asthma and
other inflammatory diseases. The challenge for scientists is to identify
factors that control this process, with the ultimate goal of developing
therapeutic strategies to reverse the progressive increase in disease.
Our studies are focused on antigen-presenting cells such as dendritic
cells (DCs) or macrophages, as they are known to direct the T cell
responses to antigen throughout life, presumably including the pre- and
post-natal period. In addition, we have developed transgenic models for
evaluating T cell functional capacity at different ages, and in
different environmental conditions, e.g. spleen or lymph node vs. lung
or intestine in naïve mice or those with allergic airway disease. Our
findings support the concept that it is not only the innate immune
system that directs T cell responses, but also that T cell responses
shape the development of the innate immune system.
Lab Rotation Projects:
Elucidation of Factors that Determine Resistance or Susceptibility to
Allergic Asthma
The focus of work is on early life events (either pre-natal or early
post-natal) that can result in T and B cell tolerance or immunity. Our
hypothesis is that the environment in neonatal mice (determined by
maternal immunity or passive transfer of antigen) is critical to
immunological outcome. Thus, we are studying the development of
functional capacity to present or recognize antigen in early life by
antigen presenting cells (primarily Dendritic Cells or Macrophages), or
T and B cells, respectively. Our preliminary data suggests that maternal
transfer of allergen can protect offspring, whereas (depending on
whether the exposure is pre- versus post-natal) maternal immunity can
promote resistance or susceptibility to development allergic airway
disease. The goals of our current projects are to define the cellular
and molecular mechanisms responsible, and studies along these lines
achievable within the time frame of a rotation will be pursued.
Puddington Publications
Selected Publications (trainees in bold):
Selander DM, Lingenheld EG, Schramm CM, Zhu L and Puddington
L. Maternal breast milk antigen induces development of allergen-specific
regulatory T cells to protect offspring from development of allergic
airway disease, in preparation.
Matson AP, Zhu L, Lingenheld EG, Schramm CM, Clark RB, Breen E,
Selander DM and Puddington L. The impact of maternal immunity on
resistance to development of allergic airway disease, submitted.
Brammer C, Lingenheld EG, Tanner C, Cose S, Pizzo E,
Khanna K, Zhu L and Puddington L. Lung antigen presenting cells induce T
cell activation in the absence of clonal expansion: Novel strategy for
control of mucosal T cell function, submitted.
Schramm CM, Puddington L, Wu C, Guernsey L, Gharaee-Kermani M, Phan SH,
Thrall RS. Chronic inhaled ovalbumin exposure induces antigen-dependent
but not antigen-specific inhalational tolerance in a murine model of
allergic airway disease. Am J Pathol. 2004 Jan;164(1):295-304.
Lee SK, Kalinowski JF, Jastrzebski SL, Puddington L, Lorenzo JA.
Interleukin-7 is a direct inhibitor of in vitro osteoclastogenesis.
Endocrinology. 2003 Aug;144(8):3524-31.
Laky K, Lewis JM, Tigelaar RE, Puddington L. Distinct
requirements for IL-7 in development of TCRγδ
cells during fetal and adult life. J Immunol. 2003 Apr
15;170(8):4087-94.
Wu CA, Puddington L, Whiteley HE, Yiamouyiannis CA, Schramm CM,
Mohammadu F, Thrall RS. Murine cytomegalovirus infection alters Th1/Th2
cytokine expression, decreases airway eosinophilia, and enhances mucus
production in allergic airway disease. J Immunol. 2001 Sep
1;167(5):2798-807.
Laky K, Lefrancois L, Lingenheld EG, Ishikawa H, Lewis JM, Olson
S, Suzuki K, Tigelaar RE, Puddington L. Enterocyte expression of
interleukin 7 induces development of γδ T
cells and Peyer's patches. J Exp Med. 2000 May 1;191(9):1569-80.
Schramm CM, Puddington L, Yiamouyiannis CA, Lingenheld EG, Whiteley HE,
Wolyniec WW, Noonan TC, Thrall RS. Proinflammatory roles of T-cell
receptor (TCR)γδ and TCRαβ
lymphocytes in a murine model of asthma. Am J Respir Cell Mol Biol. 2000
Feb;22(2):218-25.
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